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Sample records for adhesion molecule-1 expression

  1. Adiponectin Enhances Intercellular Adhesion Molecule-1 Expression and Promotes Monocyte Adhesion in Human Synovial Fibroblasts

    PubMed Central

    Chen, Hsien-Te; Tsou, Hsi-Kai; Chen, Jui-Chieh; Shih, James Meng-Kun; Chen, Yen-Jen; Tang, Chih-Hsin

    2014-01-01

    Adiponectin is a protein hormone secreted predominantly by differentiated adipocytes and is involved in energy homeostasis. Adiponectin expression is significantly high in the synovial fluid of patients with osteoarthritis (OA). Intercellular adhesion molecule-1 (ICAM-1) is an important adhesion molecule that mediates monocyte adhesion and infiltration during OA pathogenesis. Adiponectin-induced expression of ICAM-1 in human OA synovial fibroblasts (OASFs) was examined by using qPCR, flow cytometry and western blotting. The intracellular signaling pathways were investigated by pretreated with inhibitors or transfection with siRNA. The monocyte THP-1 cell line was used for an adhesion assay with OASFs. Stimulation of OASFs with adiponectin induced ICAM-1 expression. Pretreatment with AMP-activated protein kinase (AMPK) inhibitors (AraA and compound C) or transfection with siRNA against AMPKα1 and two AMPK upstream activator- liver kinase B1 (LKB1) and calmodulin-dependent protein kinase II (CaMKII) diminished the adiponectin-induced ICAM-1 expression. Stimulation of OASFs with adiponectin increased phosphorylation of LKB1, CaMKII, AMPK, and c-Jun, resulting in c-Jun binding to AP-1 element of ICAM-1 promoter. In addition, adiponectin-induced activation of the LKB1/CaMKII, AMPK, and AP-1 pathway increased the adhesion of monocytes to the OASF monolayer. Our results suggest that adiponectin increases ICAM-1 expression in human OASFs via the LKB1/CaMKII, AMPK, c-Jun, and AP-1 signaling pathway. Adiponectin-induced ICAM-1 expression promoted the adhesion of monocytes to human OASFs. These findings may provide a better understanding of the pathogenesis of OA and can utilize this knowledge to design a new therapeutic strategy. PMID:24667577

  2. Significance of platelet endothelial cell adhesion molecule-1 (PECAM-1) and intercellular adhesion molecule-1 (ICAM-1) expressions in preeclamptic placentae.

    PubMed

    Goksu Erol, Azize Yasemin; Nazli, Mumtaz; Elis Yildiz, Sevda

    2012-08-01

    Although preeclampsia (PE) is one of the most important problems affecting pregnant women, etiologic factors in its development are still unclear. We aimed to investigate the expression levels of platelet endothelial cell adhesion molecule-1 (PECAM-1) and intercellular adhesion molecule-1 (ICAM-1) in preeclamptic and control healthy placentas. Placental tissue samples were obtained after delivery from patients diagnosed with PE, and from normal term pregnants and analyzed by immunohistochemistry for the expression levels of the two adhesion molecules PECAM-1 and ICAM-1. A strong expression of PECAM-1 in endothelial cells lining the vessel walls of placental villi in placentas of control group was found, but the intensity of PECAM-1 expression was highly reduced in placentas of PE group (p = 0.017). Conversely, a strong expression of ICAM-1 was observed in placental villi in PE, significantly higher than that of normal placentas (p = 0.005). The findings of a decrease of PECAM-1 expression and an increase of ICAM-1 expression in preeclamptic placenta suggest the existence of functional roles of these adhesion molecules in the pathophysiology of PE, probably by contributing to the reduced trophoblast invasion and the increased vascular damage, respectively. Inhibiting ICAM-1 (i.e., with ICAM-1 monoclonal antibody) and promoting PECAM-1 expression may be good therapeutic approaches to prevent PE symptoms in the future.

  3. Gamma knife irradiation increases cerebral endothelial expression of intercellular adhesion molecule 1 and E-selectin.

    PubMed

    Sharp, Christopher D; Jawahar, Ajay; Warren, April C; Elrod, John W; Nanda, Anil; Alexander, J Steven

    2003-07-01

    Alterations in multiple functions of the microvasculature occur in response to gamma irradiation and are thought to contribute to radiation-induced end organ damage by inducing inflammatory responses, particularly leukocyte infiltration into the affected area. Endothelial cell adhesion molecules (ECAMs) mediate leukocyte adhesion and migration. Here, we validate a method to study the effect of Leksell gamma knife stereotactic radiosurgery on the expression of ECAMs on human cerebral endothelium at 0, 24, 48, and 72 hours after irradiation. A human brain endothelial cell line (IHEC) was cultured on 12-mm coverslips and subjected to 50 Gy of collimated gamma irradiation with the Leksell gamma knife (Elekta Instruments, Inc., Atlanta, GA). Lactate dehydrogenase release was measured at 24, 48, and 72 hours after irradiation and caspase-3 at 24, 48, 72, 96, and 120 hours. ECAM expression was measured at postirradiation intervals of 0, 24, 48, and 72 hours by cell enzyme-linked immunoabsorbent assay. We used a cell irradiator composed of two chambers. The upper chamber holds the coverslips firmly in place while they are immersed in media. The lower chamber is connected to a peristaltic pump, which pumps water into the chamber and maintains the media in the upper chamber at 37 degrees C through convection. None of the ECAMs tested was significantly elevated compared with the control basally. Twenty-four hours after irradiation, intercellular adhesion molecule 1 was significantly elevated on brain endothelial cells but there was no significant elevation of E-selectin. Vascular cell adhesion molecule 1 was increased slightly but not significantly and decreased at 48 hours. At 72 hours, E-selectin expression was significantly increased; intercellular adhesion molecule 1 and vascular cell adhesion molecule 1 were not altered relative to sham controls. Increased ECAM expression and lactate dehydrogenase release support the idea that the cerebral microvasculature undergoes an

  4. Intercellular Adhesion Molecule-1 Expression by Skeletal Muscle Cells Augments Myogenesis

    PubMed Central

    Goh, Qingnian; Dearth, Christopher L.; Corbett, Jacob T.; Pierre, Philippe; Chadee, Deborah N.; Pizza, Francis X.

    2014-01-01

    We previously demonstrated that the expression of intercellular adhesion molecule-1 (ICAM-1) by skeletal muscle cells after muscle overload contributes to ensuing regenerative and hypertrophic processes in skeletal muscle. The objective of the present study is to reveal mechanisms through which skeletal muscle cell expression of ICAM-1 augments regenerative and hypertrophic processes of myogenesis. This was accomplished by genetically engineering C2C12 myoblasts to stably express ICAM-1, and by inhibiting the adhesive and signaling functions of ICAM-1 through the use of a neutralizing antibody or cell penetrating peptide, respectively. Expression of ICAM-1 by cultured skeletal muscle cells augmented myoblast-myoblast adhesion, myotube formation, myonuclear number, myotube alignment, myotube-myotube fusion, and myotube size without influencing the ability of myoblasts to proliferate or differentiate. ICAM-1 augmented myotube formation, myonuclear accretion, and myotube alignment through a mechanism involving adhesion-induced activation of ICAM-1 signaling, as these dependent measures were reduced via antibody and peptide inhibition of ICAM-1. The adhesive and signaling functions of ICAM-1 also facilitated myotube hypertrophy through a mechanism involving myotube-myotube fusion, protein synthesis, and Akt/p70s6k signaling. Our findings demonstrate that ICAM-1 expression by skeletal muscle cells augments myogenesis, and establish a novel mechanism through which the inflammatory response facilitates growth processes in skeletal muscle. PMID:25281303

  5. Intercellular adhesion molecule-1 expression by skeletal muscle cells augments myogenesis.

    PubMed

    Goh, Qingnian; Dearth, Christopher L; Corbett, Jacob T; Pierre, Philippe; Chadee, Deborah N; Pizza, Francis X

    2015-02-15

    We previously demonstrated that the expression of intercellular adhesion molecule-1 (ICAM-1) by skeletal muscle cells after muscle overload contributes to ensuing regenerative and hypertrophic processes in skeletal muscle. The objective of the present study is to reveal mechanisms through which skeletal muscle cell expression of ICAM-1 augments regenerative and hypertrophic processes of myogenesis. This was accomplished by genetically engineering C2C12 myoblasts to stably express ICAM-1, and by inhibiting the adhesive and signaling functions of ICAM-1 through the use of a neutralizing antibody or cell penetrating peptide, respectively. Expression of ICAM-1 by cultured skeletal muscle cells augmented myoblast-myoblast adhesion, myotube formation, myonuclear number, myotube alignment, myotube-myotube fusion, and myotube size without influencing the ability of myoblasts to proliferate or differentiate. ICAM-1 augmented myotube formation, myonuclear accretion, and myotube alignment through a mechanism involving adhesion-induced activation of ICAM-1 signaling, as these dependent measures were reduced via antibody and peptide inhibition of ICAM-1. The adhesive and signaling functions of ICAM-1 also facilitated myotube hypertrophy through a mechanism involving myotube-myotube fusion, protein synthesis, and Akt/p70s6k signaling. Our findings demonstrate that ICAM-1 expression by skeletal muscle cells augments myogenesis, and establish a novel mechanism through which the inflammatory response facilitates growth processes in skeletal muscle. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Intercellular adhesion molecule-1 expression by skeletal muscle cells augments myogenesis

    SciTech Connect

    Goh, Qingnian; Dearth, Christopher L.; Corbett, Jacob T.; Pierre, Philippe; Chadee, Deborah N.; Pizza, Francis X.

    2015-02-15

    We previously demonstrated that the expression of intercellular adhesion molecule-1 (ICAM-1) by skeletal muscle cells after muscle overload contributes to ensuing regenerative and hypertrophic processes in skeletal muscle. The objective of the present study is to reveal mechanisms through which skeletal muscle cell expression of ICAM-1 augments regenerative and hypertrophic processes of myogenesis. This was accomplished by genetically engineering C2C12 myoblasts to stably express ICAM-1, and by inhibiting the adhesive and signaling functions of ICAM-1 through the use of a neutralizing antibody or cell penetrating peptide, respectively. Expression of ICAM-1 by cultured skeletal muscle cells augmented myoblast–myoblast adhesion, myotube formation, myonuclear number, myotube alignment, myotube–myotube fusion, and myotube size without influencing the ability of myoblasts to proliferate or differentiate. ICAM-1 augmented myotube formation, myonuclear accretion, and myotube alignment through a mechanism involving adhesion-induced activation of ICAM-1 signaling, as these dependent measures were reduced via antibody and peptide inhibition of ICAM-1. The adhesive and signaling functions of ICAM-1 also facilitated myotube hypertrophy through a mechanism involving myotube–myotube fusion, protein synthesis, and Akt/p70s6k signaling. Our findings demonstrate that ICAM-1 expression by skeletal muscle cells augments myogenesis, and establish a novel mechanism through which the inflammatory response facilitates growth processes in skeletal muscle. - Highlights: • We examined mechanisms through which skeletal muscle cell expression of ICAM-1 facilitates events of in vitro myogenesis. • Expression of ICAM-1 by cultured myoblasts did not influence their ability to proliferate or differentiate. • Skeletal muscle cell expression of ICAM-1 augmented myoblast fusion, myotube alignment, myotube–myotube fusion, and myotube size. • ICAM-1 augmented myogenic processes through

  7. Expression of intercellular adhesion molecule-1 by myofibers in mdx mice.

    PubMed

    Torres-Palsa, Maria J; Koziol, Matthew V; Goh, Qingnian; Cicinelli, Peter A; Peterson, Jennifer M; Pizza, Francis X

    2015-11-01

    We investigated the extent to which intercellular adhesion molecule-1 (ICAM-1), a critical protein of the inflammatory response, is expressed in skeletal muscles of mdx mice (a murine model of Duchenne muscular dystrophy). Muscles were collected from control and mdx mice at 2-24 weeks of age and analyzed for ICAM-1 expression by means of Western blot and immunofluorescence. Western blot revealed higher expression of ICAM-1 in mdx compared with control muscles through 24 weeks of age. In contrast to control muscles, ICAM-1 was expressed on the membrane of damaged, regenerating, and normal myofibers of mdx mice. CD11b+ myeloid cells also expressed ICAM-1 in mdx muscles, and CD11b+ cells were closely associated with the membrane of myofibers expressing ICAM-1. These findings support a paradigm in which ICAM-1 and its localization to myofibers in muscles of mdx mice contributes to the dystrophic pathology. © 2015 Wiley Periodicals, Inc.

  8. EXPRESSION OF INTERCELLULAR ADHESION MOLECULE-1 BY MYOFIBERS IN mdx MICE

    PubMed Central

    TORRES-PALSA, MARIA J.; KOZIOL, MATTHEW V.; GOH, QINGNIAN; CICINELLI, PETER A.; PETERSON, JENNIFER M.; PIZZA, FRANCIS X.

    2017-01-01

    Introduction We investigated the extent to which intercellular adhesion molecule-1 (ICAM-1), a critical protein of the inflammatory response, is expressed in skeletal muscles of mdx mice (a murine model of Duchenne muscular dystrophy). Methods Muscles were collected from control and mdx mice at 2–24 weeks of age and analyzed for ICAM-1 expression by means of Western blot and immunofluorescence. Results Western blot revealed higher expression of ICAM-1 in mdx compared with control muscles through 24 weeks of age. In contrast to control muscles, ICAM-1 was expressed on the membrane of damaged, regenerating, and normal myofibers of mdx mice. CD11b+ myeloid cells also expressed ICAM-1 in mdx muscles, and CD11b+ cells were closely associated with the membrane of myofibers expressing ICAM-1. Conclusions These findings support a paradigm in which ICAM-1 and its localization to myofibers in muscles of mdx mice contributes to the dystrophic pathology. PMID:25728314

  9. Amphiregulin enhances intercellular adhesion molecule-1 expression and promotes tumor metastasis in human osteosarcoma

    PubMed Central

    Liu, Ju-Fang; Tsao, Ya-Ting; Hou, Chun-Han

    2015-01-01

    Osteosarcoma is a common, high malignant, and metastatic bone cancer. Amphiregulin (AREG) has been associated with cancer cellular activities. However, the effect of AREG on metastasis activity in human osteosarcoma cells has yet to be determined. We determined that AREG increases the expression of intercellular adhesion molecule-1 (ICAM-1) through PI3K/Akt signaling pathway via its interaction with the epidermal growth factor receptor, thus resulting in the enhanced cell migration of osteosarcoma. Furthermore, AREG stimulation increased the association of NF-κB to ICAM-1 promoter which then up-regulated ICAM-1 expression. Finally, we observed that shRNA silencing of AREG decreased osteosarcoma metastasis in vivo. Our findings revealed a relationship between osteosarcoma metastatic potential and AREG expression and the modulating effect of AREG on ICAM-1 expression. PMID:26503469

  10. Amphiregulin enhances intercellular adhesion molecule-1 expression and promotes tumor metastasis in human osteosarcoma.

    PubMed

    Liu, Ju-Fang; Tsao, Ya-Ting; Hou, Chun-Han

    2015-12-01

    Osteosarcoma is a common, high malignant, and metastatic bone cancer. Amphiregulin (AREG) has been associated with cancer cellular activities. However, the effect of AREG on metastasis activity in human osteosarcoma cells has yet to be determined. We determined that AREG increases the expression of intercellular adhesion molecule-1 (ICAM-1) through PI3K/Akt signaling pathway via its interaction with the epidermal growth factor receptor, thus resulting in the enhanced cell migration of osteosarcoma. Furthermore, AREG stimulation increased the association of NF-κB to ICAM-1 promoter which then up-regulated ICAM-1 expression. Finally, we observed that shRNA silencing of AREG decreased osteosarcoma metastasis in vivo. Our findings revealed a relationship between osteosarcoma metastatic potential and AREG expression and the modulating effect of AREG on ICAM-1 expression.

  11. Androgen exposure increases human monocyte adhesion to vascular endothelium and endothelial cell expression of vascular cell adhesion molecule-1.

    PubMed

    McCrohon, J A; Jessup, W; Handelsman, D J; Celermajer, D S

    1999-05-04

    Male sex is an independent risk factor for coronary artery disease. Owing to the importance of monocyte adhesion to endothelial cells in the development of atherosclerosis, we hypothesized that androgens might promote this process. We therefore studied the effects of the nonaromatizable androgen dihydrotestosterone (DHT) on human monocyte adhesion to human endothelial cells and on endothelial cell-surface expression of adhesion molecules. Human umbilical vein endothelial cells (HUVECs) were grown to confluence in media supplemented with postmenopausal female serum, then exposed for 48 hours to either DHT (40 and 400 nmol/L), with or without the androgen receptor blocker hydroxyflutamide (HF) (4 micromol/L); HF alone; or vehicle control (ethanol 0.1%). Human monocytes obtained by elutriation were incubated for 1 hour with the HUVECs at 37 degrees C, and adhesion was measured by light microscopy. Compared with vehicle control, monocyte adhesion was increased in the androgen-treated HUVECs in a dose-dependent manner (116+/-6% and 128+/-3% for DHT 40 and 400 nmol/L respectively; P<0.001). HF blocked this increase (P>/=0.3 compared with control). Surface expression of endothelial cell adhesion molecules was measured by ELISA and revealed an increased expression of vascular cell adhesion molecule-1 (VCAM-1) in the DHT-treated HUVECs (125+/-5% versus 100+/-4% in controls; P=0.002), an effect also antagonized by HF (P>/=0.3 compared with controls). Furthermore, the DHT-related increase in adhesion was completely blocked by coincubation with anti-VCAM-1 antibody. Comparable results were obtained in arterial endothelial cells and in endothelium stimulated with the cytokine tumor necrosis factor-alpha. Androgen exposure is associated with increased human monocyte adhesion to endothelial cells, a proatherogenic effect mediated at least in part by an increased endothelial cell-surface expression of VCAM-1.

  12. Control of islet intercellular adhesion molecule-1 expression by interferon-alpha and hypoxia.

    PubMed

    Chakrabarti, D; Huang, X; Beck, J; Henrich, J; McFarland, N; James, R F; Stewart, T A

    1996-10-01

    The ability of interferon-alpha (IFN-alpha) to induce the adhesion molecules that characterize the islets of patients with type I diabetes has been investigated. We have found that all tested recombinant IFN-as will induce major histocompatibility complex (MHC) class I on arterial endothelial cells. Some but not all IFN-as will induce intercellular adhesion molecule-1 (ICAM-1). However, there is only a transient and modest increase in VCAM on arterial endothelial cells. IFN-alpha has very little effect on endothelial MHC class II expression but will induce these proteins on monocytes. Thus, there is a close concordance between the biological actions of IFN-alpha and the appearance of those adhesion molecules induced in the islets of patients with type I diabetes. IFN-alpha is also produced in normal human islets during short-term cultures, probably as a result of the ischemia present at the center of the islet. This induction of IFN-alpha by hypoxia may explain the previously reported spontaneous induction of ICAM-1 in human islets and may also be a contributing factor to the failure of islet grafts.

  13. Differential effects of heme oxygenase isoforms on heme mediation of endothelial intracellular adhesion molecule 1 expression.

    PubMed

    Wagener, F A; da Silva, J L; Farley, T; de Witte, T; Kappas, A; Abraham, N G

    1999-10-01

    Heme oxygenase (HO), by catabolizing heme to bile pigments, down-regulates cellular hemoprotein, hemoglobin, and heme; the latter generates pro-oxidant products, including free radicals. Two HO isozymes, the products of distinct genes, have been described; HO-1 is the inducible isoform, whereas HO-2 is suggested to be constitutively expressed. We studied the inducing effect of several metal compounds (CoCl(2), stannic mesoporphyrin, and heme) on HO activity. Additionally, we studied HO-1 expression in experimental models of adhesion molecule expression produced by heme in endothelial cells, and the relationship of HO-1 expression to the induced adhesion molecules. Flow cytometry analysis showed that heme induces intracellular adhesion molecule 1 (ICAM-1) expression in a concentration (10-100 microM)- and time (1-24 h)-dependent fashion in human umbilical vein endothelial cells. Pretreatment with stannic mesoporphyrin, an inhibitor of HO activity, caused a 2-fold increase in heme-induced ICAM-1 expression. In contrast, HO induction by CoCl(2) decreased heme-induced ICAM-1 expression by 33%. To examine the contribution of HO-1 and HO-2 to endothelial HO activity, specific antisense oligonucleotides (ODNs) of each isoform were tested for their specificity to inhibit HO activity in cells exposed to heme. Endothelial cells exposed to heme elicited increased HO activity, which was prevented (70%) by HO-1 antisense ODNs. HO-2 antisense ODN inhibited heme-induced HO activity by 21%. Addition of HO-1 antisense ODNs prevented heme degradation and resulted in elevation of microsomal heme. Western blot analysis showed that HO-1 antisense ODNs selectively inhibited HO-1 protein and failed to inhibit HO-2 protein. Incubation of endothelial cells with HO-1 antisense enhanced heme-dependent increase of ICAM-1. In contrast, addition of HO-2 antisense to endothelial cells failed to increase adhesion molecules. The role of glutathione, an important antioxidant, was examined on heme

  14. Effect of Cell Adhesion Molecule 1 Expression on Intracellular Granule Movement in Pancreatic α Cells.

    PubMed

    Yokawa, Satoru; Furuno, Tadahide; Suzuki, Takahiro; Inoh, Yoshikazu; Suzuki, Ryo; Hirashima, Naohide

    2016-09-01

    Although glucagon secreted from pancreatic α cells plays a role in increasing glucose concentrations in serum, the mechanism regulating glucagon secretion from α cells remains unclear. Cell adhesion molecule 1 (CADM1), identified as an adhesion molecule in α cells, has been reported not only to communicate among α cells and between nerve fibers, but also to prevent excessive glucagon secretion from α cells. Here, we investigated the effect of CADM1 expression on the movement of intracellular secretory granules in α cells because the granule transport is an important step in secretion. Spinning disk microscopic analysis showed that granules moved at a mean velocity of 0.236 ± 0.010 μm/s in the mouse α cell line αTC6 that expressed CADM1 endogenously. The mean velocity was significantly decreased in CADM1-knockdown (KD) cells (mean velocity: 0.190 ± 0.016 μm/s). The velocity of granule movement decreased greatly in αTC6 cells treated with the microtubule-depolymerizing reagent nocodazole, but not in αTC6 cells treated with the actin-depolymerizing reagent cytochalasin D. No difference in the mean velocity was observed between αTC6 and CADM1-KD cells treated with nocodazole. These results suggest that intracellular granules in pancreatic α cells move along the microtubule network, and that CADM1 influences their velocity.

  15. Intercellular adhesion molecule-1 (ICAM-1) expression is upregulated in autoimmune murine lupus nephritis.

    PubMed Central

    Wuthrich, R. P.; Jevnikar, A. M.; Takei, F.; Glimcher, L. H.; Kelley, V. E.

    1990-01-01

    Intercellular adhesion molecule-1 (ICAM-1) is a cell-surface protein regulating interactions among immune cells. To determine whether altered expression of ICAM-1 occurs in autoimmune lupus nephritis, we studied ICAM-1 expression in kidneys of normal and autoimmune MRL-lpr and (NZBX NZW)F1 (NZB/W) mice. By immunoperoxidase staining, ICAM-1 is constitutively expressed at low levels in proximal tubules (PT), endothelium and interstitial cells in normal C3H/FeJ mice. In nephritic MRL-lpr and NZB/W kidneys, staining for ICAM-1 is increased in the PT, particularly in the brush border, and is prominent in the glomerular mesangium and the endothelium of large vessels. By Western blot analysis, ICAM-1 is not detected in the urine of normal BALB/c and C3H/FeJ or autoimmune MRL-lpr. By Northern blot analysis, nephritic MRL-lpr and NZB/W have a two- to fivefold increase in steady state levels of ICAM-1 transcripts in the kidney as compared with normal or prenephritic mice. This is paralleled by an increase in MHC class II transcripts. In cultured PT cells, ICAM-1 is expressed at basal levels in PT and is increased by the cytokines interferon-gamma, IL-1 alpha, and TNF-alpha. Thus cytokine-mediated upregulation of ICAM-1 in lupus nephritis may promote interaction of immune cells with renal tissue. The predominant apical expression of ICAM-1 opposite to the basolateral Ia expression suggests a novel role for this adhesion molecule in PT. Images Figure 1 Figure 2 Figure 3 Figure 6 Figure 7 PMID:1968316

  16. Inhibitory effects of nicotinamide on intercellular adhesion molecule-1 expression on cultured human thyroid cells.

    PubMed Central

    Hiromatsu, Y; Sato, M; Tanaka, K; Ishisaka, N; Kamachi, J; Nonaka, K

    1993-01-01

    We investigated the effects of nicotinamide and 3-aminobenzamide (3-AB), inhibitors of poly (ADP ribose) synthetase, on phytohaemagglutinin (PHA)- or interferon-gamma (IFN-gamma)-induced intercellular adhesion molecule-1 (ICAM-1) expression on cultured thyroid cells from patients with Graves' disease. Primary cultured thyroid cells were incubated for 3 days with IFN-gamma (10-800 U/ml) or PHA (1-50 micrograms/ml) in the presence of nicotinamide, 3-AB, superoxide dismutase or catalase. The surface expression of ICAM-1 was measured by flow cytometry. Nicotinamide and 3-AB dose-dependently inhibited the induction of ICAM-1 expression by IFN-gamma or PHA on thyroid cells. Neither catalase nor superoxide dismutase, which are free-radical scavengers, inhibited the expression of ICAM-1 on thyroid cells. Our data suggest that the mechanism of the suppression of ICAM-1 expression on thyroid cells by nicotinamide is not likely to be due to the free radical scavenging. Further studies are indicated to elucidate whether the inhibition of ICAM-1 by these drugs may result in the suppression of autoimmune reaction in the thyroid gland. PMID:7903279

  17. Arsenite enhances tumor necrosis factor-{alpha}-induced expression of vascular cell adhesion molecule-1

    SciTech Connect

    Tsou, T.-C. . E-mail: tctsou@nhri.org.tw; Yeh, Szu Ching; Tsai, E.-M.; Tsai, F.-Y.; Chao, H.-R.; Chang, Louis W.

    2005-11-15

    Epidemiological studies demonstrated a high association of vascular diseases with arsenite exposure. We hypothesize that arsenite potentiates the effect of proinflammatory cytokines on vascular endothelial cells, and hence contributes to atherosclerosis. In this study, we investigated the effect of arsenite and its induction of glutathione (GSH) on vascular cell adhesion molecule-1 (VCAM-1) protein expression in human umbilical vein endothelial cells (HUVECs) in response to tumor necrosis factor-{alpha} (TNF-{alpha}), a typical proinflammatory cytokine. Our study demonstrated that arsenite pretreatment potentiated the TNF-{alpha}-induced VCAM-1 expression with up-regulations of both activator protein-1 (AP-1) and nuclear factor-{kappa}B (NF-{kappa}B). To elucidate the role of GSH in regulation of AP-1, NF-{kappa}B, and VCAM-1 expression, we employed L-buthionine (S,R)-sulfoximine (BSO), a specific {gamma}-glutamylcysteine synthetase ({gamma}-GCS) inhibitor, to block intracellular GSH synthesis. Our investigation revealed that, by depleting GSH, arsenite attenuated the TNF-{alpha}-induced VCAM-1 expression as well as a potentiation of AP-1 and an attenuation of NF-{kappa}B activations by TNF-{alpha}. Moreover, we found that depletion of GSH would also attenuate the TNF-{alpha}-induced VCAM-1 expression with a down-regulation of the TNF-{alpha}-induced NF-{kappa}B activation and without significant effect on AP-1. On the other hand, the TNF-{alpha}-induced VCAM-1 expression could be completely abolished by inhibition of AP-1 or NF-{kappa}B activity, suggesting that activation of both AP-1 and NF-{kappa}B was necessary for VCAM-1 expression. In summary, we demonstrate that arsenite enhances the TNF-{alpha}-induced VCAM-1 expression in HUVECs via regulation of AP-1 and NF-{kappa}B activities in a GSH-sensitive manner. Our present study suggested a potential mechanism for arsenite in the induction of vascular inflammation and vascular diseases via modulating the actions

  18. Mouse cells expressing human intercellular adhesion molecule-1 are susceptible to infection by coxsackievirus A21.

    PubMed Central

    Shafren, D R; Dorahy, D J; Greive, S J; Burns, G F; Barry, R D

    1997-01-01

    Competitive viral binding assays have revealed previously that coxsackievirus A21 (CAV21) and human rhinovirus 14 (HRV14) share a common cell surface receptor. More recently, intercellular adhesion molecule-1 (ICAM-1) has been identified as the cellular receptor for HRV-14. Also, anti-ICAM-1 monoclonal antibodies (MAbs) blocked infection by HRV14, CAV13, CAV18, and CAV21, suggesting that these viruses share this receptor; however, this has never been established by more direct methods. In this study we show conclusively that CAV21 binds to ICAM-1 and that MAbs directed against the N-terminal domain of the molecule inhibit this attachment. Furthermore, we show that the specific interaction between ICAM-1 and 160S CAV21 virions induces formation of 135S A particles. Finally, we show transfection of normally nonsusceptible mouse L cells with human ICAM-1 cDNA renders them susceptible to infection by CAV21. PMID:8985417

  19. Experimental Cerebral Malaria Develops Independently of Endothelial Expression of Intercellular Adhesion Molecule-1 (ICAM-1)*

    PubMed Central

    Ramos, Theresa N.; Bullard, Daniel C.; Darley, Meghan M.; McDonald, Kristin; Crawford, David F.; Barnum, Scott R.

    2013-01-01

    Cerebral malaria (CM) is a severe clinical complication of Plasmodium falciparum malaria infection and is characterized by a high fatality rate and neurological damage. Sequestration of parasite-infected red blood cells in brain microvasculature utilizes host- and parasite-derived adhesion molecules and is an important factor in the development of CM. ICAM-1, an alternatively spliced adhesion molecule, is believed to be critical on endothelial cells for infected red blood cell sequestration in CM. Using ICAM-1 mutant mice, we found that the full-length ICAM-1 isoform is not required for development of murine experimental CM (ECM) and that ECM phenotype varies with the combination of ICAM-1 isoforms expressed. Furthermore, we observed development of ECM in transgenic mice expressing ICAM-1 only on leukocytes, indicating that endothelial cell expression of this adhesion molecule is not required for disease pathogenesis. We propose that ICAM-1-dependent cellular aggregation, independent of ICAM-1 expression on the cerebral microvasculature, contributes to ECM. PMID:23493396

  20. Experimental cerebral malaria develops independently of endothelial expression of intercellular adhesion molecule-1 (icam-1).

    PubMed

    Ramos, Theresa N; Bullard, Daniel C; Darley, Meghan M; McDonald, Kristin; Crawford, David F; Barnum, Scott R

    2013-04-19

    Cerebral malaria (CM) is a severe clinical complication of Plasmodium falciparum malaria infection and is characterized by a high fatality rate and neurological damage. Sequestration of parasite-infected red blood cells in brain microvasculature utilizes host- and parasite-derived adhesion molecules and is an important factor in the development of CM. ICAM-1, an alternatively spliced adhesion molecule, is believed to be critical on endothelial cells for infected red blood cell sequestration in CM. Using ICAM-1 mutant mice, we found that the full-length ICAM-1 isoform is not required for development of murine experimental CM (ECM) and that ECM phenotype varies with the combination of ICAM-1 isoforms expressed. Furthermore, we observed development of ECM in transgenic mice expressing ICAM-1 only on leukocytes, indicating that endothelial cell expression of this adhesion molecule is not required for disease pathogenesis. We propose that ICAM-1-dependent cellular aggregation, independent of ICAM-1 expression on the cerebral microvasculature, contributes to ECM.

  1. Expression of HLA-ABC, HLA-DR and intercellular adhesion molecule-1 in oesophageal carcinoma.

    PubMed Central

    Rockett, J C; Darnton, S J; Crocker, J; Matthews, H R; Morris, A G

    1995-01-01

    AIM--To examine the expression of HLA-ABC and HLA-DR major histocompatibility (MHC) antigens and intercellular adhesion molecule (ICAM)-1 in normal, inflamed, metaplastic, and neoplastic oesophageal tissue and in freshly disaggregated tumours. METHODS--Sequential sections of frozen tissue and cytospins of freshly disaggregated tumour were stained using the ABC peroxidase system and monoclonal antibodies specific for HLA-ABC, HLA-DR and ICAM-1. RESULTS--Normal oesophageal tissue showed positive staining for HLA-ABC in the basal layers of the oesophageal squamous epithelium and on the epithelial cells of the submucosal oesophageal glands. HLA-DR and ICAM-1 were not detected in either of these cell types. In 20 of 37 (54%) carcinomas HLA-ABC was expressed weakly, with heterogeneous expression in nine (24%). Two tumours showed strong expression of HLA-ABC, but 15 of 37 (41%) were negative. HLA-DR and ICAM-1 were expressed weakly in six of 37 (16%) carcinomas without correlation with each other or with the expression of HLA-ABC. CONCLUSIONS--HLA-ABC is absent from a high proportion of oesophageal carcinomas (41%) and is otherwise variably and weakly expressed with strong expression in only a small fraction (3%). In other carcinomas there is a higher level of HLA-ABC expression. This discrepancy may partly explain the aggressive nature of oesophageal carcinomas. HLA-DR and ICAM-1 are not normally expressed on those cells from which oesophageal carcinomas are thought to arise. The limited expression found here could suggest a partial or inhibited immune response against oesophageal carcinoma. In vivo repressive factors may be involved. Images PMID:7665697

  2. Feverfew extracts and the sesquiterpene lactone parthenolide inhibit intercellular adhesion molecule-1 expression in human synovial fibroblasts.

    PubMed

    Piela-Smith, T H; Liu, X

    2001-05-01

    Previous studies have shown that extracts of the aromatic herb feverfew (Tanacetum parthenium) and one of its bioactive components, parthenolide, have anti-inflammatory properties in vivo and in vitro. We examined both crude feverfew extracts and purified parthenolide for their ability to modulate adhesion molecule expression in human synovial fibroblasts. Pretreatment of synovial fibroblasts with either feverfew extracts or purified parthenolide could inhibit the expression of intercellular adhesion molecule-1 (ICAM-1) induced by the cytokines IL-1 (up to 95% suppression), TNF-alpha (up to 93% suppression), and, less strongly, interferon-gamma (up to 39% suppression). Inhibition of ICAM-1 was dose and time dependent; as little as a 30-min pretreatment with feverfew resulted in inhibition of ICAM-1. The decrease in ICAM-1 expression was accompanied by a decrease in T-cell adhesion to the treated fibroblasts. Other herbal extracts with reported anti-inflammatory effects were similarly tested and did not decrease ICAM-1 expression. The modulation of adhesion molecule expression may be an additional mechanism by which feverfew mediates anti-inflammatory effects. Copyright 2001 Academic Press.

  3. PRIMING EFFECT OF HOMOCYSTEINE ON INDUCIBLE VASCULAR CELL ADHESION MOLECULE-1 EXPRESSION IN ENDOTHELIAL CELLS

    PubMed Central

    Séguin, Chantal; Abid, Md. Ruhul; Spokes, Katherine C.; Schoots, Ivo G; Brkovic, Alexandre; Sirois, Martin G.; Aird, William C.

    2017-01-01

    Hyperhomocysteinemia is an independent risk factor for the development of atherosclerosis, as well as for arterial and venous thrombosis. However, the mechanisms through which elevated circulating levels of homocysteine cause vascular injury and promote thrombosis remain unclear. Here, we tested the hypothesis that homocysteine (Hcy) sensitizes endothelial cells to the effect of inflammatory mediators. Human umbilical vein endothelial cells (HUVEC) were incubated with Hcy 1.0 mM for varying time points, and then treated in the absence or presence of 1.5 U/ml thrombin or 10 ng/ml lipopolysaccharide (LPS). Hcy alone had no effect on the expression of vascular cell adhesion molecule (VCAM)-1. However, Hcy enhanced thrombin- and LPS-mediated induction of VCAM-1 mRNA and protein levels. Consistent with these results, pretreatment of HUVEC with Hcy resulted in a two-fold increase in LSP-mediated induction of leukocyte adhesion. The latter effect was significantly inhibited by anti-VCAM-1 antibodies. Together, these findings suggest that Hcy sensitizes HUVEC to the effect of inflammatory mediators thrombin and LPS, at least in part through VCAM-1 expression and function. PMID:18406566

  4. Epidermal Expression of Intercellular Adhesion Molecule 1 is Not a Primary Inducer of Cutaneous Inflammation in Transgenic Mice

    NASA Astrophysics Data System (ADS)

    Williams, Ifor R.; Kupper, Thomas S.

    1994-10-01

    Keratinocytes at sites of cutaneous inflammation have increased expression of intercellular adhesion molecule 1 (ICAM-1), a cytokine-inducible adhesion molecule which binds the leukocyte integrins LFA-1 and Mac-1. Transgenic mice were prepared in which the expression of mouse ICAM-1 was targeted to basal keratinocytes by using the human K14 keratin promoter. The level of constitutive expression attained in the transgenic mice exceeded the peak level of ICAM-1 expression induced on nontransgenic mouse keratinocytes in vitro by optimal combinations of interferon γ and tumor necrosis factor α or in vivo by proinflammatory stimuli such as phorbol 12-myristate 13-acetate. In vitro adhesion assays demonstrated that cultured transgenic keratinocytes were superior to normal keratinocytes as a substrate for the LFA-1-dependent binding of mouse T cells, confirming that the transgene-encoded ICAM-1 was expressed in a functional form. However, the high level of constitutive ICAM-1 expression achieved on keratinocytes in vivo in these transgenic mice did not result in additional recruitment of CD45^+ leukocytes into transgenic epidermis, nor did it elicit dermal inflammation. Keratinocyte ICAM-1 expression also did not potentiate contact-hypersensitivity reactions to epicutaneous application of haptens. The absence of a spontaneous phenotype in these transgenic mice was not the result of increased levels of soluble ICAM-1, since serum levels of soluble ICAM-1 were equal in transgenic mice and controls. We conclude that elevated ICAM-1 expression on keratinocytes cannot act independently to influence leukocyte trafficking and elicit cutaneous inflammation.

  5. De novo expression of intercellular adhesion molecule 1 (ICAM-1, CD54) in pancreas cancer.

    PubMed

    Schwaeble, W; Kerlin, M; Meyer zum Büschenfelde, K H; Dippold, W

    1993-01-21

    We examined the expression of intercellular--adhesion molecule-I (ICAM-I, CD54) in 6 surgically removed pancreatic tumors and 8 pancreatic tumor cell lines. Immunohistochemistry revealed a varying percentage of ICAM-I-positive pancreas tumor cells, while normal pancreatic tissue (except for slight reactivity of endothelial cells) was not stained. The presence of the ICAM-I molecule on the cell surface and the expression of ICAM-I mRNA were investigated for 8 different pancreatic tumor cell lines. Three of these (Capan-I, Capan-2, QGP-I) expressed ICAM-I constitutively. In 4 of the ICAM-I-negative pancreas cancer cell lines, it was possible to induce a remarkable expression of ICAM-I by incubating the cells in the presence of inflammatory cytokines, whereas one cell line, 818-4, remained ICAM-I-negative. The responsiveness to either IFN-gamma, TNF-alpha, or IL-I beta treatment was shown to vary from cell line to cell line, indicating complex mechanisms that regulate the expression of ICAM-I at both, the transcriptional and the post-transcriptional level. Interestingly, ICAM-I is shed by pancreatic tumor cells, since soluble sICAM-I was detected in the cell-culture supernatants. In comparison with normal sera, the mean level of sICAM-I in sera of patients with pancreas carcinoma is elevated 2-fold.

  6. MicroRNA-221 controls expression of intercellular adhesion molecule-1 in epithelial cells in response to Cryptosporidium parvum infection

    PubMed Central

    Gong, Ai-Yu; Hu, Guoku; Zhou, Rui; Liu, Jun; Feng, Yaoyu; Soukup, Garrett A.; Chen, Xian-Ming

    2011-01-01

    Cryptosporidium parvum is a protozoan parasite that infects gastrointestinal epithelial cells and causes diarrheal disease in humans and animals globally. Pathological changes following C. parvum infection include crypt hyperplasia, a modest inflammatory reaction with increased infiltration of lymphocytes into intestinal mucosa. Expression of adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1), on infected epithelial cell surfaces may facilitate adhesion and recognition of lymphocytes at infection sites. MicroRNAs (miRNAs) are small RNA molecules of 23 nucleotides that negatively regulate protein-coding gene expression via translational suppression or mRNA degradation. We recently reported that microRNA-221 (miR-221) regulates ICAM-1 translation through targeting the ICAM-1 3′-untranslated region (UTR). In this study, we tested the role of miR-221 in regulating ICAM-1 expression in epithelial cells in response to C. parvum infection using an in vitro model of human biliary cryptosporidiosis. Up-regulation of ICAM-1 at both message and protein levels was detected in epithelial cells following C. parvum infection. Inhibition of ICAM-1 transcription with actinomycin D could only partially block C. parvum-induced ICAM-1 expression at the protein level. Cryptosporidium parvum infection decreased miR-221 expression in infected epithelial cells. When cells were transfected with a luciferase reporter construct covering the miR-221 binding site in the ICAM-1 3′-UTR and then exposed to C. parvum, an enhanced luciferase activity was detected. Transfection of miR-221 precursor abolished C. parvum-stimulated ICAM-1 protein expression. In addition, expression of ICAM-1 on infected epithelial cells facilitated epithelial adherence of co-cultured Jurkat cells. These results indicate that miR-221-mediated translational suppression controls ICAM-1 expression in epithelial cells in response to C. parvum infection. PMID:21236259

  7. Effects of dexamethasone on intercellular adhesion molecule 1 expression and inflammatory response in necrotizing acute pancreatitis in rats.

    PubMed

    Ramudo, Laura; Yubero, Sara; Manso, Manuel A; Sanchez-Recio, Javier; Weruaga, Eduardo; De Dios, Isabel

    2010-10-01

    Adhesion molecules are involved in the inflammatory response during acute pancreatitis (AP). We investigated the effect of dexamethasone (Dx) on intercellular adhesion molecule 1 (ICAM-1) expression during AP and its consequences on leukocyte recruitment and pancreatic damage. Acute pancreatitis was induced in rats by 3.5% sodium taurocholate for 3 hours and 6 hours. Dexamethasone (1 mg/kg) was administered either 30 minutes before or 1 hour after inducing AP. Messenger RNA ICAM-1 expression in pancreas and lung, membrane-bound ICAM-1 in acinar cells, and ICAM-1 plasma levels were analyzed. Histological examination of the pancreas and neutrophil infiltration in pancreas and lung were also measured. Prophylactic and therapeutic administration of Dx down-regulated ICAM-1 expression in pancreas and lung from early AP. Dexamethasone given before AP reduced the pancreatic damage, but lung inflammation was not prevented. Therapeutic Dx treatment was ineffective in avoiding leukocyte recruitment into the pancreas and lung in rats with AP. High ICAM-1 concentration was found in plasma during AP, which was not reduced by Dx treatments. Dexamethasone down-regulates ICAM-1 expression, but it does not completely prevent leukocyte recruitment during sodium taurocholate-induced AP.

  8. Inducible expression of vascular cell adhesion molecule-1 by vascular smooth muscle cells in vitro and within rabbit atheroma.

    PubMed Central

    Li, H.; Cybulsky, M. I.; Gimbrone, M. A.; Libby, P.

    1993-01-01

    Vascular cell adhesion molecule-1 (VCAM-1), a mononuclear leukocyte adhesion molecule, is expressed in cultured vascular endothelial cells activated by cytokines and is induced in rabbit aortic endothelium in vivo within 1 week after initiation of an atherogenic diet. We now demonstrate that vascular smooth muscle cells can also express VCAM-1 in rabbit atherosclerotic lesions in vivo and in response to cytokines in vitro. Immunohistochemical staining of aortas from rabbits fed a 0.3% cholesterol-containing diet revealed that a portion of smooth muscle cells within intimal foam cell-rich lesions expressed VCAM-1. The intimal VCAM-1-expressing cells localized predominantly in regions above the internal elastic lamina. These VCAM-1-positive cells had the typical spindle shape of smooth muscle cells but had reduced alpha-actin expression in comparison to normal medial smooth muscle cells, and did not bear markers for endothelium, macrophages, and T cells. In culture, rabbit aortic smooth muscle cells expressed VCAM-1 mRNA and protein in a time- and concentration-dependent fashion when exposed to interferon-gamma or Gram-negative bacterial lipopolysaccharide. Cultured human vascular smooth muscle cells also expressed VCAM-1 mRNA and protein in response to lipopolysaccharide, interferon-gamma, and interleukin-4. The monokines interleukin-1 alpha and tumor necrosis factor-alpha did not induce VCAM-1 expression in either rabbit or human vascular smooth muscle cells. Inducible VCAM-1 expression by vascular smooth muscle cells in vivo during hypercholesterolemia and in vitro in response to certain cytokines suggests a broader range of VCAM-1 functions in vascular biology than heretofore appreciated. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:7504883

  9. Expression of intercellular adhesion molecule 1 (ICAM-1) on the human oviductal epithelium and mediation of lymphoid cell adherence.

    PubMed

    Utreras, E; Ossandon, P; Acuña-Castillo, C; Varela-Nallar, L; Müller, C; Arraztoa, J A; Cardenas, H; Imarai, M

    2000-09-01

    The epithelium of the human oviduct expresses the major histocompatibility complex (MHC) class II and shows endocytic properties towards luminal antigens. Therefore, the epithelial cells might behave as antigen-presenting cells, inducing a local immune response. The activation of antigen-specific T cells not only requires presentation of the peptide antigen by MHC class II, but also the presence of co-stimulatory molecules in the antigen-presenting cells. Therefore, the expression of the intercellular adhesion molecule 1 (ICAM-1) was examined in the epithelium of the human oviduct. Most oviducts showed epithelial ICAM-1 expression, as assessed by immunocytochemistry, western blot analysis and RT-PCR assay, and the expression was restricted to the luminal border of ciliated and secretory cells. Interferon gamma, interleukin 1 and lipopolysaccharide treatments increased the percentage of ICAM-1-positive cells in primary cultures, indicating that the expression of ICAM-1 in the oviduct might be upregulated in vivo by inflammatory cytokines or bacterial infections. Binding assays between allogenic phytohaemagglutinin-activated lymphocytes and epithelial monolayers expressing ICAM-1 demonstrated that this molecule stimulated lymphocyte adherence. The presence of ICAM-1, in addition to MHC class II, supports the putative role of the oviductal epithelium in antigen presentation. The exclusive apical distribution of ICAM-1 indicates that T-cell activation would occur in a polarized manner. Binding of lymphoid cells to the surface of the oviductal epithelium may help to retain these immune cells that are required for the clearance of pathogens.

  10. Folate deficiency and aberrant expression of cell adhesion molecule 1 are potential indicators of prognosis in laryngeal squamous cell carcinoma

    PubMed Central

    Chang, Hao; Ma, Min; Ma, Rui; Zhang, Chao; Zeng, Wei; Xing, Lu Qi

    2016-01-01

    The etiology of laryngeal squamous cell carcinoma (LSCC) has not yet been adequately examined. Therefore, the present study aimed to investigate the association between serum folate deficiency and abnormal expression of the cell adhesion molecule 1 (CADM1) protein in the progression of LSCC. Samples were collected from 60 patients with LSCC and 30 healthy people. Radioimmunoassays and immunohistochemical staining were performed to measure serum folate levels and CADM1 protein expression, respectively. The results demonstrated that CADM1 expression in LSCC specimens was significantly lower than in adjacent normal tissues (χ2=28.229, P<0.001), which was associated with histological differentiation and clinical stage (P=0.010 and 0.020, respectively). Levels of serum folate in patients with LSCC were significantly lower than those observed in healthy individuals (P=0.002). Furthermore, TSLCl expression and serum folate levels were positively correlated in LSCC (r=0.642, P=0.001). Thus, the present study determined that decreased CADM1 protein expression and low levels of serum folate were correlated with an increased severity of LSCC. PMID:28105160

  11. Intercellular adhesion molecule-1 expression in experimental alcoholic liver disease: relationship to endotoxemia and TNF alpha messenger RNA.

    PubMed

    Nanji, A A; Griniuviene, B; Yacoub, L K; Fogt, F; Tahan, S R

    1995-02-01

    We used the intragastric feeding rat model for alcoholic liver disease to evaluate the relationship among intercellular adhesion molecule-1 (ICAM-1) expression, tumor necrosis factor-alpha (TNF-alpha), plasma endotoxin, and inflammatory changes in the liver. Rats were fed different dietary fats (saturated fat, corn oil, and fish oil) with ethanol; control rats were fed isocaloric amounts of dextrose instead of ethanol. At sacrifice the following were evaluated: liver pathologic changes, TNF-alpha mRNA by reverse transcription-PCR, plasma endotoxin, and ICAM-1 by immunohistochemistry and immunoblot analysis. Upregulation of ICAM-1 in endothelial lining cells in central and portal veins was observed in rats showing evidence of pathologic changes. Rats fed fish oil and ethanol, which exhibited the most severe inflammation, also showed hepatocyte ICAM-1 staining. The presence of ICAM-1 staining, in general, correlated with the level of TNF-alpha mRNA expression and plasma endotoxin levels. Upregulation of ICAM-1 in rats fed ethanol may contribute to the inflammatory changes seen in this model. The association between ICAM-1 upregulation and endotoxin and TNF-alpha mRNA suggests a role for these mediators in the inflammatory process in alcoholic liver injury.

  12. Renoprotective effects of berberine and its potential effect on the expression of β-arrestins and intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in streptozocin-diabetic nephropathy rats.

    PubMed

    Tang, Li-Qin; Ni, Wei-Jian; Cai, Ming; Ding, Hai-Hua; Liu, Sheng; Zhang, Shan-Tang

    2016-09-01

    Berberine has been shown to exert protective effects against diabetic nephropathy (DN), but the mechanisms involved have not been fully characterized. The aim of the present study was to explore the effects of berberine on the expression of β-arrestins, intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in DN rat kidneys and investigate the underlying molecular mechanisms. To create the DN model, rats fed a high-fat and high-glucose diet were injected with a single dose of streptozotocin (35 mg/kg, i.p.). Then, DN rats were either treated or not with berberine (50, 100, 200 mg/kg per day, i.g., 8 weeks). Periodic acid-Schiff staining was used to evaluate renal histopathological changes. Renal tissue levels of β-arrestin 1 and β-arrestin 2 were determined by Western blot analysis, whereas immunohistochemistry was used to determine renal ICAM-1 and VCAM-1 levels. Berberine (100, 200 mg/kg) ameliorated the histopathological changes in the diabetic kidney. Western blot analysis revealed significant increases in ICAM-1 and VCAM-1 levels in the kidneys of DN rats, which were reversed by treatment with 100 and 200 mg/kg berberine. In addition, berberine treatment (50, 100, 200 mg/kg) increased diabetic-induced decreases in β-arrestin 1 and β-arrestin 2. Berberine exhibited renoprotective effects in DN rats. The underlying molecular mechanisms may be associated with changes in the levels and regulation of β-arrestin expression, as well as ICAM-1 and VCAM-1 levels in the rat kidney. © 2015 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

  13. Effects of Chinese yellow wine on nitric oxide synthase and intercellular adhesion molecule-1 expressions in rat vascular endothelial cells.

    PubMed

    Zhao, Fei; Ji, Zheng; Chi, Jufang; Tang, Weiliang; Zhai, Xiaoya; Meng, Liping; Guo, Hangyuan

    2016-02-01

    The objective of this study was to determine similarities in the effect of yellow wine as compared to statin and the possibility that yellow wine inhibits tumour necrosis factor-α (TNF-α)-induced nitric oxide (NO) synthesis, endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), and intercellular adhesion molecule-1 (ICAM-1) in cultured rat vascular endothelial cells (VECs). We isolated VECs, and cultivated and purified Sprague Dawley (SD) rat thoracic aortas in vitro. We selected the optimal wine concentration using clonogenic and MTT assays to measure cell survival. Next, we divided the cells into 9 groups: (1) control, (2) TNF-α, (3) TNF-α + rosuvastatin (10 μmol/L), (4) TNF-α + ethanol 0.5%, (5) TNF-α + yellow wine 0.5%, (6) TNF-α + ethanol 1.0%, (7) TNF-α + yellow wine 1.0%, (8) TNF-α + ethanol 1.5%, and (9) TNF-α + yellow wine 1.5% and they were given the corresponding treatment for 24 h. We determined NO production with nitrate reductase. We then measured eNOS activity, and detected eNOS, iNOS, and ICAM-1 protein levels by Western blotting. Compared with the TNF-α group, NO production, eNOS activity, and eNOS protein expression in the rosuvastatin, and yellow wine 1.0%, and 1.5% groups were significantly increased. Protein expression of iNOS and ICAM-1 in the rosuvastatin, yellow wine 1.0%, and 1.5% groups were significantly decreased. Compared with the rosuvastatin group, eNOS, iNOS, and ICAM-1 protein expression in the yellow wine (0.5% -1.5%) groups were significantly different. Treatment with yellow wine increased NO production, eNOS activity, and eNOS protein expression, which decreases iNOS and ICAM-1 protein expression. We conclude that yellow wine may have similar beneficial effects as rosuvastatin on the cardiovascular system. These effects may be attributed to their anti-atherosclerotic actions.

  14. Exosomes from iPSCs Delivering siRNA Attenuate Intracellular Adhesion Molecule-1 Expression and Neutrophils Adhesion in Pulmonary Microvascular Endothelial Cells.

    PubMed

    Ju, Zhihai; Ma, Jinhui; Wang, Chen; Yu, Jie; Qiao, Yeru; Hei, Feilong

    2017-04-01

    The pro-inflammatory activation of pulmonary microvascular endothelial cells resulting in continuous expression of cellular adhesion molecules, and subsequently recruiting primed neutrophils to form a firm neutrophils-endothelium (PMN-EC) adhesion, has been examined and found to play a vital role in acute lung injury (ALI). RNA interference (RNAi) is a cellular process through harnessing a natural pathway silencing target gene based on recognition and subsequent degradation of specific mRNA sequences. It opens a promising approach for precision medicine. However, this application was hampered by many obstacles, such as immunogenicity, instability, toxicity problems, and difficulty in across the biological membrane. In this study, we reprogrammed urine exfoliated renal epithelial cells into human induced pluripotent stem cells (huiPSCs) and purified the exosomes (Exo) from huiPSCs as RNAi delivery system. Through choosing the episomal system to deliver transcription factors, we obtained a non-integrating huiPSCs. Experiments in both vitro and vivo demonstrated that these huiPSCs possess the pluripotent properties. The exosomes of huiPSCs isolated by differential centrifugation were visualized by transmission electron microscopy (TEM) showing a typical exosomal appearance with an average diameter of 122 nm. Immunoblotting confirmed the presence of the typical exosomal markers, including CD63, TSG 101, and Alix. Co-cultured PKH26-labeled exosomes with human primary pulmonary microvascular endothelial cells (HMVECs) confirmed that they could be internalized by recipient cells at a time-dependent manner. Then, electroporation was used to introduce siRNA against intercellular adhesion molecule-1 (ICAM-1) into exosomes to form an Exo/siRNA compound. The Exo/siRNA compound efficiently delivered the target siRNA into HMVECs causing selective gene silencing, inhibiting the ICAM-1 protein expression, and PMN-EC adhesion induced by lipopolysaccharide (LPS). These data suggest

  15. Rhein inhibits the expression of vascular cell adhesion molecule 1 in human umbilical vein endothelial cells with or without lipopolysaccharide stimulation.

    PubMed

    Hu, Gang; Liu, Jiang; Zhen, Yong-Zhan; Wei, Jie; Qiao, Yue; Lin, Ya-Jun; Tu, Ping

    2013-01-01

    Reducing the expression of endothelial cell adhesion molecules (ECAMs) is known to decrease inflammation-induced vascular complications. In this study, we explored whether rhein can reduce the inflammation-induced expression of ECAMs in human umbilical vein endothelial cells (HUVECs) with or without lipopolysaccharide (LPS) stimulation. HUVECs were treated with different concentrations of rhein with or without 2.5 μg/ml LPS stimulation. Cell viability was assayed using the MTT method. Real-time PCR and Western blot analysis were used to measure the transcription and expression levels of ECAMs, including intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E-SELECTIN and related signaling proteins. The results indicated that rhein (0-20 μmol/L) and LPS (0-10 μg/ml) had no effect on the viability of HUVECs. LPS could promote the expression of VCAM-1, ICAM-1 and E-SELECTIN. Rhein appeared to target VCAM-1, ICAM-1 and E-SELECTIN, with the transcription and expression of all three factors being reduced by the rhein treatment (10 and 20 μmol/L). The transcription and expression of VCAM-1 were also reduced by treatment with rhein (10 and 20 μmol/L) in the presence of LPS stimulation. In conclusion, rhein treatment reduced the expression of VCAM-1 in HUVECs via a p38-dependent pathway.

  16. Effects of nitrogen dioxide on the expression of intercellular adhesion molecule-1, neutrophil adhesion, and cytotoxicity: studies in human bronchial epithelial cells.

    PubMed

    Ayyagari, Vijayalakshmi N; Januszkiewicz, Adolph; Nath, Jayasree

    2007-02-01

    Nitrogen Dioxide (NO2) is a product of high-temperature combustion and an environmental oxidant of concern. We have recently reported that early changes in NO2-exposed human bronchial epithelial cells are causally linked to increased generation of proinflammatory mediators, such as nitric oxide/nitrite and cytokines like interleukin (IL)-1beta, tumor necrosis factor (TNF)-alpha and IL-8. The objective of the present in vitro study was to further delineate the cellular mechanisms of NO2-mediated toxicity, and to define the nature of cell death that ensues upon exposure of normal human bronchial epithelial (NHBE) cells to a brief high dose of NO2. Our results demonstrate that the NHBE cells undergo apoptotic cell death during the early post-NO2 period, but this is independent of any significant increase in caspase-3 activity. However, necrotic cell death was more prevalent at later time intervals. Interestingly, an increased expression of HO-1, a redox-sensitive stress protein, was observed in NO2-exposed NHBE cells at 24 h. Since neutrophils (PMNs) play an active role in acute lung inflammation and resultant oxidative injury, we also investigated changes in human PMN-NHBE cell interactions. As compared to normal cells, increased adhesion of PMNs to NO2-exposed cells was observed, which resulted in an increased NHBE cell death. The latter was also increased in the presence of IL-8 and TNF-alpha + interferon (IFN)-gamma, which correlated with upregulation of intercellular adhesion molecule-1 (ICAM-1). Our results confirmed an involvement of nitric oxide (NO) in NO2-induced cytotoxicity. By using NO synthase inhibitors such as L-NAME and 3-aminoguanidine (AG), a significant decrease in cell death, PMN adhesion, and ICAM-1 expression was observed. These findings indicate a role for the L-arginine/NO synthase pathway in the observed NO2-mediated toxicity in NHBE cells. Therapeutic strategies aimed at controlling excess generation of NO and/or inflammatory cytokines may

  17. Interferon gamma regulates platelet endothelial cell adhesion molecule 1 expression and neutrophil infiltration into herpes simplex virus- infected mouse corneas

    PubMed Central

    1996-01-01

    In a mouse model of herpes simplex virus (HSV) 1 corneal infection, tissue destruction results from a CD4+ T cell-mediated chronic inflammation, in which interleukin 2 and interferon (IFN) gamma are requisite inflammatory mediators and polymorphonuclear leukocytes (PMN) are the predominant infiltrating cells. In vivo neutralization of IFN- gamma relieved inflammation at least in part through a specific block of PMN extravasation into HSV-1-infected corneas. Intercellular adhesion molecule (ICAM) 1 and platelet endothelial cell adhesion molecule (PECAM) 1 were upregulated on the vascular endothelium of inflamed corneas. Reduced PMN extravasation in anti-IFN-gamma-treated mice was associated with a dramatic reduction of PECAM-1 but not ICAM-1 expression on vascular endothelium. PMN accumulated in the lumen of corneal vessels after in vivo IFN-gamma neutralization. PECAM-1 was readily detectable on PMN inside the vessels but was not detectable on PMN that extravasated into the infected cornea. Moreover, flow cytometric analysis revealed reduced PECAM-1 expression but elevated major histocompatibility complex class I expression on PMN that recently extravasated into the peritoneal cavity when compared with PMN in the peripheral blood. We conclude that IFN-gamma contributes to HSV- 1-induced corneal inflammation by facilitating PMN infiltration; this appears to be accomplished through upregulation of PECAM-1 expression on the vascular endothelium; and PMN downregulate PECAM-1 expression during the process of extravasation. PMID:8879215

  18. Sesamin attenuates intercellular cell adhesion molecule-1 expression in vitro in TNF-alpha-treated human aortic endothelial cells and in vivo in apolipoprotein-E-deficient mice.

    PubMed

    Wu, Wen-Huey; Wang, Shu-Huei; Kuan, I-I; Kao, Ya-Shi; Wu, Pei-Jhen; Liang, Chan-Jung; Chien, Hsiung-Fei; Kao, Chiu-Hua; Huang, Ching-Jang; Chen, Yuh-Lien

    2010-09-01

    Sesame lignans have antioxidative and anti-inflammatory properties. We focused on the effects of the lignans sesamin and sesamol on the expression of endothelial-leukocyte adhesion molecules in tumor necrosis factor-alpha (TNF-alpha)-treated human aortic endothelial cells (HAECs). When HAECs were pretreated with sesamin (10 or 100 microM), the TNF-alpha-induced expression of intercellular cell adhesion molecule-1 (ICAM-1) was significantly reduced (35 or 70% decrease, respectively) by Western blotting. Sesamol was less effective at inhibiting ICAM-1 expression (30% decrease at 100 microM). Sesamin and sesamol reduced the marked TNF-alpha-induced increase in human antigen R (HuR) translocation and the interaction between HuR and the 3'UTR of ICAM-1 mRNA. Both significantly reduced the binding of monocytes to TNF-alpha-stimulated HAECs. Sesamin significantly attenuated TNF-alpha-induced ICAM-1 expression and cell adhesion by downregulation of extracellular signal-regulated kinase 1/2 and p38. Furthermore, in vivo, sesamin attenuated intimal thickening and ICAM-1 expression seen in aortas of apolipoprotein-E-deficient mice. Taken together, these data suggest that sesamin inhibits TNF-alpha-induced extracellular signal-regulated kinase/p38 phosphorylation, nuclear translocation of NF-kappaB p65, cytoplasmic translocalization of HuR and thereby suppresses ICAM-1 expression, resulting in reduced adhesion of leukocytes. These results also suggest that sesamin may prevent the development of atherosclerosis and inflammatory responses.

  19. αdβ2 Integrin Is Expressed on Human Eosinophils and Functions as an Alternative Ligand for Vascular Cell Adhesion Molecule 1 (VCAM-1)

    PubMed Central

    Grayson, Mitchell H.; Van der Vieren, Monica; Sterbinsky, Sherry A.; Michael Gallatin, W.; Hoffman, Patricia A.; Staunton, Donald E.; Bochner, Bruce S.

    1998-01-01

    The β2 family of integrins, CD11a, CD11b, CD11c, and αd, are expressed on most leukocytes. We show that the newest member of this family, αd, is expressed on human eosinophils in peripheral blood, and surface expression can be upregulated within minutes by phorbol ester or calcium ionophore A23187. Culture of eosinophils with interleukin 5 (IL-5) leads to a two- to fourfold increase in αd levels by 3–7 d without a change in α4 integrin expression. Eosinophils isolated from late phase bronchoalveolar lavage fluids express αd at levels similar to that seen after 3 d of IL-5 culture. Regarding αdβ2 ligands, in both freshly isolated and IL-5–cultured eosinophils, as well as αdβ2-transfected Chinese hamster ovary cells, αdβ2 can function as a ligand for vascular cell adhesion molecule 1 (VCAM-1). This conclusion is based on the ability of monoclonal antibodies to αd, β2, or VCAM-1 to block cell attachment in static adhesion assays. In experiments with eosinophils, the relative contribution of αdβ2 integrin– mediated adhesion is enhanced after IL-5 culture. These experiments demonstrate that αdβ2 is an alternative ligand for VCAM-1, and this integrin may play a role in eosinophil adhesion to VCAM-1 in states of chronic inflammation. PMID:9841932

  20. The 18-kDa Translocator Protein Inhibits Vascular Cell Adhesion Molecule-1 Expression via Inhibition of Mitochondrial Reactive Oxygen Species

    PubMed Central

    Joo, Hee Kyoung; Lee, Yu Ran; Kang, Gun; Choi, Sunga; Kim, Cuk-Seong; Ryoo, Sungwoo; Park, Jin Bong; Jeon, Byeong Hwa

    2015-01-01

    Translocator protein 18 kDa (TSPO) is a mitochondrial outer membrane protein and is abundantly expressed in a variety of organ and tissues. To date, the functional role of TSPO on vascular endothelial cell activation has yet to be fully elucidated. In the present study, the phorbol 12-myristate 13-acetate (PMA, 250 nM), an activator of protein kinase C (PKC), was used to induce vascular endothelial activation. Adenoviral TSPO overexpression (10–100 MOI) inhibited PMA-induced vascular cell adhesion molecule-1 (VCAM-1) and intracellular cell adhesion molecule-1 (ICAM-1) expression in a dose dependent manner. PMA-induced VCAM-1 expressions were inhibited by Mito-TEMPO (0.1–0.5 μM), a specific mitochondrial antioxidants, and cyclosporin A (1–5 μM), a mitochondrial permeability transition pore inhibitor, implying on an important role of mitochondrial reactive oxygen species (ROS) on the endothelial activation. Moreover, adenoviral TSPO overexpression inhibited mitochondrial ROS production and manganese superoxide dismutase expression. On contrasts, gene silencing of TSPO with siRNA increased PMA-induced VCAM-1 expression and mitochondrial ROS production. Midazolam (1–50 μM), TSPO ligands, inhibited PMA-induced VCAM-1 and mitochondrial ROS production in endothelial cells. These results suggest that mitochondrial TSPO can inhibit PMA-induced endothelial inflammation via suppression of VCAM-1 and mitochondrial ROS production in endothelial cells. PMID:26608360

  1. MicroRNA126 contributes to granulocyte colony-stimulating factor-induced hematopoietic progenitor cell mobilization by reducing the expression of vascular cell adhesion molecule 1.

    PubMed

    Salvucci, Ombretta; Jiang, Kan; Gasperini, Paola; Maric, Dragan; Zhu, Jinfang; Sakakibara, Shuhei; Espigol-Frigole, Georgina; Wang, Shushang; Tosato, Giovanna

    2012-06-01

    Mobilization of hematopoietic stem/progenitor cells from the bone marrow to the peripheral blood by granulocyte colony-stimulating factor is the primary means to acquire stem cell grafts for hematopoietic cell transplantation. Since hematopoietic stem/progenitor cells represent a minority of all blood cells mobilized by granulocyte colony-stimulating factor, the underlying mechanisms need to be understood in order to develop selective drugs. We analyzed phenotypic, biochemical and genetic changes in bone marrow cell populations from granulocyte colony-stimulating factor-mobilized and control mice, and linked such changes to effective mobilization of hematopoietic stem/progenitor cells. We show that granulocyte colony-stimulating factor indirectly reduces expression of surface vascular cell adhesion molecule 1 on bone marrow hematopoietic stem/progenitor cells, stromal cells and endothelial cells by promoting the accumulation of microRNA-126 (miR126)-containing microvescicles in the bone marrow extracellular compartment. We found that hematopoietic stem/progenitor cells, stromal cells and endothelial cells readily incorporate these miR126-loaded microvescicles, and that miR126 represses vascular cell adhesion molecule 1 expression on bone marrow hematopoietic stem/progenitor cells, stromal cells and endothelial cells. In line with this, miR126-null mice displayed a reduced mobilization response to granulocyte colony-stimulating factor. Our results implicate miR126 in the regulation of hematopoietic stem/progenitor cell trafficking between the bone marrow and peripheral sites, clarify the role of vascular cell adhesion molecule 1 in granulocyte colony-stimulating factor-mediated mobilization, and have important implications for improved approaches to selective mobilization of hematopoietic stem/progenitor cells.

  2. Magnolol reduced TNF-α-induced vascular cell adhesion molecule-1 expression in endothelial cells via JNK/p38 and NF-κB signaling pathways.

    PubMed

    Liang, Chan-Jung; Lee, Chiang-Wen; Sung, Hsin-Ching; Chen, Yung-Hsiang; Wang, Shu-Huei; Wu, Pei-Jhen; Chiang, Yao-Chang; Tsai, Jaw-Shiun; Wu, Chau-Chung; Li, Chi-Yuan; Chen, Yuh-Lien

    2014-01-01

    Expression of cell adhesion molecules by the endothelium and the attachment of leukocytes to these cells play major roles in inflammation and cardiovascular disorders. Magnolol, a major active component of Magnolia officinalis, has antioxidative and anti-inflammatory properties. In the present study, the effects of magnolol on the expression of vascular cell adhesion molecule-1 (VCAM-1) in human aortic endothelial cells (HAECs) and the related mechanisms were investigated. TNF-α induced VCAM-1 protein expression and mRNA stability were significantly decreased in HAECs pre-treated with magnolol. Magnolol significantly reduced the phosphorylation of ERK, JNK, and p38 in TNF-α-treated HAECs. The decrease in VCAM-1 expression in response to TNF-α treatment was affected by JNK and p38 inhibitors, not by an ERK inhibitor. Magnolol also attenuates NF-κB activation and the translocation of HuR (an RNA binding protein) in TNF-α-stimulated HAECs. The VCAM-1 expression was weaker in the aortas of TNF-α-treated apo-E deficient mice with magnolol treatment. These data demonstrate that magnolol inhibits TNF-α-induced JNK/p38 phosphorylation, HuR translocation, NF-κB activation, and thereby suppresses VCAM-1 expression resulting in reduced leukocyte adhesion. Taken together, these results suggest that magnolol has an anti-inflammatory property and may play an important role in the prevention of atherosclerosis and inflammatory responses.

  3. Alterations in soluble intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in hemodialysis patients.

    PubMed

    Rabb, H; Calderon, E; Bittle, P A; Ramirez, G

    1996-02-01

    Hemodialysis (HD) patients can develop acute reactions during treatment as well as increased long-term susceptibility to infections and malignancies. Abnormalities in leukocyte adhesion may contribute to these processes. Recently, serum levels of soluble adhesion molecules have been detected in circulating blood of normal subjects and in patients with chronic renal failure. We studied the effects of a single dialysis session with new cuprophane membrane on the soluble (s) form of intracellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), two adhesion molecules with a variety of immunologic roles. Significant elevations in both sICAM-1 (523 +/- 61 v 304 +/- 45 [SEM] ng/mL, P < 0.05) and sVCAM-1 (2,055 +/- 270 v 1,189 +/- 149 ng/mL, P < 0.05) were observed in HD patients at baseline compared with controls. Both sICAM-1 and sVCAM-1 levels decreased after a 3-hour HD session (P < 0.001). Early in HD, sICAM-1 levels, though lower than predialysis, were elevated in the exit line of the dialyzer compared with entrance (339 +/- 64 v 259 +/- 53 ng/mL, P < 0.001), whereas sVCAM-1 was decreased on the exit line compared with entrance (639 +/- 90 v 932 +/- 92 ng/mL, P < 0.001). Because ICAM-1 and VCAM-1 are important for many leukocyte functions, alterations in serum levels of sICAM-1 and sVCAM-1 may play a role in the immunologic consequences of uremia and HD treatment.

  4. Expression of intercellular adhesion molecule-1 (ICAM-1) on vascular endothelial cells and renal tubular cells in the generalized Shwartzman reaction as an experimental disseminated intravascular coagulation model.

    PubMed

    Koide, N; Abe, K; Narita, K; Kato, Y; Sugiyama, T; Yoshida, T; Yokochi, T

    1997-05-01

    The participation of adhesion molecules in systemic vascular injuries of the generalized Shwartzman reaction was studied. The generalized Shwartzman reaction was induced in mice by two consecutive injections of lipopolysaccharide. Intercellular adhesion molecule-1 (ICAM-1) was expressed on vascular endothelial cells, renal tubular cells and alveolar wall in generalized Shwartzman reaction-induced mice. The preparative injection of lipopolysaccharides induced ICAM-1 expression in those cells, and the provocative injection of lipopolysaccharides for the generalized Shwartzman reaction augmented it further. The simultaneous administration of anti-gamma interferon antibody with the preparative injection of lipopolysaccharides completely inhibited ICAM-1 expression on vascular endothelial cells. The injection of recombinant gamma interferon in replacement of lipopolysaccharides resulted in ICAM-1 expression. The administration of anti-ICAM-1 antibody together with the provocative injection of lipopolysaccharides significantly blocked the apoptosis of vascular endothelial cells in generalized Shwartzman reaction-induced mice. It was suggested that ICAM-1 expression on vascular endothelial cells might be involved in systemic vascular injuries of the generalized Shwartzman reaction, and that it might be regulated by gamma interferon.

  5. Transfected HEK293 Cells Expressing Functional Recombinant Intercellular Adhesion Molecule 1 (ICAM-1) – A Receptor Associated with Severe Plasmodium falciparum Malaria

    PubMed Central

    Bengtsson, Anja; Joergensen, Louise; Barbati, Zachary R.; Craig, Alister; Hviid, Lars; Jensen, Anja T. R.

    2013-01-01

    Intercellular adhesion molecule 1 (ICAM-1) is a membrane-bound glycoprotein expressed on endothelial cells and cells of the immune system. Human ICAM-1 mediates adhesion and migration of leucocytes, and is implicated in inflammatory pathologies, autoimmune diseases and in many cancer processes. Additionally, ICAM-1 acts as receptor for pathogens like human rhinovirus and Plasmodium falciparum malaria parasites. A group of related P. falciparum erythrocyte membrane protein 1 (PfEMP1) domains, the DBLβ, mediates ICAM-1 binding of P. falciparum-infected erythrocytes. This ICAM‑1-binding phenotype has been suggested to be involved in the development of cerebral malaria. However, more studies identifying cross-reactive antibody and ICAM-1-binding epitopes and the establishment of a clinical link between DBLβ expression and e.g. cerebral malaria are needed before the DBLβ domains can be put forward as vaccine candidates and go into clinical trials. Such studies require availability of functional recombinant ICAM-1 in large quantities. In this study, we compared recombinant ICAM-1 expressed in HEK293 and COS-7 cells with mouse myeloma NS0 ICAM-1 purchased from a commercial vendor in terms of protein purity, yield, fold, ability to bind DBLβ, and relative cost. We present a HEK293 cell-based, high-yield expression and purification scheme for producing inexpensive, functional ICAM‑1. ICAM-1 expressed in HEK293 is applicable to malaria research and can also be useful in other research fields. PMID:23936131

  6. Characterization and functional analysis of the expression of intercellular adhesion molecule-1 in human papillomavirus-related disease of cervical keratinocytes.

    PubMed Central

    Coleman, N.; Greenfield, I. M.; Hare, J.; Kruger-Gray, H.; Chain, B. M.; Stanley, M. A.

    1993-01-01

    We have investigated the expression of intercellular adhesion molecule-1 (ICAM-1) in squamous neoplasia of the cervix and have noted a significant induction of the molecule in high-grade intra-epithelial lesions. Using monolayer and organotypic in vitro tissue culture systems, we have shown that there is no constitutive ICAM-1 expression on cervical keratinocytes immortalized but not transformed by human papillomavirus type 16, whereas two human papillomaviruses type 16 containing and fully transformed cervical keratinocyte lines do constitutively express the molecule. All cell types, including human papillomavirus-negative normal cervical keratinocytes, can be induced to up-regulate their expression of ICAM-1 by pro-inflammatory cytokines such as interferon-gamma. In addition, we have used an in vitro adhesion assay to show that ICAM-1:lymphocyte function antigen-1 interaction is functionally important in lymphocyte binding to cervical keratinocytes, suggesting a role for ICAM-1 in retaining and enabling functional activity of lymphocytes in the cervix in intraepithelial neoplasia. Images Figure 1 Figure 2 Figure 5 Figure 9 PMID:8102029

  7. Simple modifications to Methimazole that enhance its inhibitory effect on Tumor Necrosis Factor-α-induced Vascular Cell Adhesion Molecule-1 expression by human endothelial cells

    PubMed Central

    Alapati, Anuja; Deosarkar, Sudhir P.; Lanier, Olivia L.; Qi, Chunyan; Carlson, Grady E.; Burdick, Monica M.; Schwartz, Frank L.; McCall, Kelly D.; Bergmeier, Stephen C.; Goetz, Douglas J.

    2015-01-01

    The expression of vascular cell adhesion molecule-1 (VCAM-1) on the vascular endothelium can be increased by pro-inflammatory cytokines [e.g. tumor necrosis factor – α (TNF-α)]. VCAM-1 contributes to leukocyte adhesion to, and emigration from, the vasculature which is a key aspect of pathological inflammation. As such, a promising therapeutic approach for pathological inflammation is to inhibit the expression of VCAM-1. Methimazole [3-methyl-1, 3 imidazole-2 thione (MMI)] is routinely used for the treatment of Graves’ disease and patients treated with MMI have decreased levels of circulating VCAM-1. In this study we used cultured human umbilical vein endothelial cells (HUVEC) to investigate the effect of MMI structural modifications on TNF-α induced VCAM-1 expression. We found that addition of a phenyl ring at the 4-nitrogen of MMI yields a compound that is significantly more potent than MMI at inhibiting 24 h TNF-α-induced VCAM-1 protein expression. Addition of a para methoxy to the appended phenyl group increases the inhibition while substitution of a thiazole ring for an imidazole ring in the phenyl derivatives yields no clear difference in inhibition. Addition of the phenyl ring to MMI appears to increase toxicity as does substitution of a thiazole ring for an imidazole ring in the phenyl MMI derivatives. Each of the compounds reduced TNF-α-induced VCAM-1 mRNA expression and had a functional inhibitory effect, i.e. each inhibited monocytic cell adhesion to 24 h TNF-α-activated HUVEC under fluid flow conditions. Combined, these studies provide important insights into the design of MMI-related anti-inflammatory compounds. PMID:25641748

  8. Allergen-stimulated T lymphocytes from allergic patients induce vascular cell adhesion molecule-1 (VCAM-1) expression and IL-6 production by endothelial cells.

    PubMed Central

    Delneste, Y; Jeannin, P; Gosset, P; Lassalle, P; Cardot, E; Tillie-Leblond, I; Joseph, M; Pestel, J; Tonnel, A B

    1995-01-01

    Adhesion of inflammatory cells to endothelium is a critical step for their transvascular migration to inflammatory sites. To evaluate the relationship between T lymphocytes (TL) and vascular endothelium, supernatants from allergen-stimulated TL obtained from patients sensitive to Dermatophagoides pteronyssinus (Dpt) versus healthy subjects were added to endothelial cell (EC) cultures. TL were stimulated by autologous-activated antigen-presenting cells (APC) previously fixed in paraformaldehyde to prevent monokine secretion. Two parameters were measured: the expression of adhesion molecule and the production of IL-6. Related allergen-stimulated TL supernatants from allergic patients induced an increase of VCAM-1 and intercellular adhesion molecule-1 (ICAM-1) expression when supernatants of the control groups (TL exposed to an unrelated allergen or not stimulated or TL obtained from healthy subjects) did not. E-selectin expression was not modulated whatever the supernatant added to EC culture. IL-6 production by EC was significantly enhanced after activation with related allergen-stimulated TL supernatants from allergics compared with control supernatants. Induction of VCAM-1 expression was inhibited by adding neutralizing antibodies against IL-4, whereas IL-6 production and ICAM-1 expression were inhibited by anti-interferon-gamma (IFN-gamma) antibodies. Enhanced production of IL-4 and IFN-gamma was detected in related allergen-stimulated TL supernatants from allergic subjects compared with the different supernatants. These data suggest that allergen-specific TL present in the peripheral blood of allergic patients are of Th1 and Th2 subtypes. Their stimulation in allergic patients may lead to the activation of endothelial cells and thereby participate in leucocyte recruitment towards the inflammatory site. PMID:7542574

  9. Simple modifications to methimazole that enhance its inhibitory effect on tumor necrosis factor-α-induced vascular cell adhesion molecule-1 expression by human endothelial cells.

    PubMed

    Alapati, Anuja; Deosarkar, Sudhir P; Lanier, Olivia L; Qi, Chunyan; Carlson, Grady E; Burdick, Monica M; Schwartz, Frank L; McCall, Kelly D; Bergmeier, Stephen C; Goetz, Douglas J

    2015-03-15

    The expression of vascular cell adhesion molecule-1 (VCAM-1) on the vascular endothelium can be increased by pro-inflammatory cytokines [e.g. tumor necrosis factor-α (TNF-α)]. VCAM-1 contributes to leukocyte adhesion to, and emigration from, the vasculature which is a key aspect of pathological inflammation. As such, a promising therapeutic approach for pathological inflammation is to inhibit the expression of VCAM-1. Methimazole [3-methyl-1, 3 imidazole-2 thione (MMI)] is routinely used for the treatment of Graves׳ disease and patients treated with MMI have decreased levels of circulating VCAM-1. In this study we used cultured human umbilical vein endothelial cells (HUVEC) to investigate the effect of MMI structural modifications on TNF-α induced VCAM-1 expression. We found that addition of a phenyl ring at the 4-nitrogen of MMI yields a compound that is significantly more potent than MMI at inhibiting 24h TNF-α-induced VCAM-1 protein expression. Addition of a para methoxy to the appended phenyl group increases the inhibition while substitution of a thiazole ring for an imidazole ring in the phenyl derivatives yields no clear difference in inhibition. Addition of the phenyl ring to MMI appears to increase toxicity as does substitution of a thiazole ring for an imidazole ring in the phenyl MMI derivatives. Each of the compounds reduced TNF-α-induced VCAM-1 mRNA expression and had a functional inhibitory effect, i.e. each inhibited monocytic cell adhesion to 24h TNF-α-activated HUVEC under fluid flow conditions. Combined, these studies provide important insights into the design of MMI-related anti-inflammatory compounds.

  10. Green tea polyphenol epigallocatechin-3-gallate attenuates TNF-α-induced intercellular adhesion molecule-1 expression and monocyte adhesion to retinal pigment epithelial cells.

    PubMed

    Thichanpiang, Peeradech; Wongprasert, Kanokpan

    2015-01-01

    Epigallocatechin-3-gallate (EGCG) is a major polyphenol component of green tea (Camellia sinensis) and demonstrates anti-oxidant, anticancer and anti-inflammatory properties. EGCG has been shown to protect retinal pigment epithelium (RPE) against oxidative stress-induced cell death. The pathogenesis of diseases in the retina is usually initiated by local inflammation at the RPE cell layer, and inflammation is mostly associated with leukocyte migration and the secretion of pro-inflammatory cytokines. Whether EGCG can modulate the cytokine-induced inflammatory response of RPE, particularly leukocyte migration, has not been clearly elucidated, and was therefore the objective of this study. ARPE-19 cells were cultured with different concentrations of TNF-α in the presence or absence of EGCG to different time points. Intracellular reactive oxygen species (ROS) levels were determined. Intercellular adhesion molecule (ICAM)-1 and phosphor-NF-κB and IκB expression were determined by Western blot analysis. Phosphor-NF-κB nuclear translocation and monocyte-RPE adhesion were investigated using immunofluorescence confocal laser scanning microscopy. Scanning electron microscopy (SEM) was carried out to further determine the ultrastructure of monocyte-RPE adhesion. The results demonstrated that TNF-α modulated inflammatory effects in ARPE-19 by induction of ROS and up-regulation of ICAM-1 expression. Moreover, TNF-α-induced phosphor-NF-κB nuclear translocation, increased phosphor-NF-κB expression and IκB degradation, and increased the degree of monocyte-RPE adhesion. Pretreating the cells with EGCG ameliorated the inflammatory effects of TNF-α. The results indicated that EGCG significantly exerts anti-inflammatory effects in ARPE-19 cells, partly as a suppressor of TNF-α signaling and that the inhibition was mediated via the NF-κB pathway.

  11. Bordetella pertussis infection of human respiratory epithelial cells up-regulates intercellular adhesion molecule-1 expression: role of filamentous hemagglutinin and pertussis toxin.

    PubMed

    Ishibashi, Yoshio; Nishikawa, Akemi

    2002-09-01

    Adhesion molecules on respiratory epithelial cells play a critical role in inflammatory cell recruitment and accumulation at sites of inflammation. Bordetella pertussis colonizes the human respiratory tract by infecting epithelial cells, leading to an inflammatory response. In this study, the role of bacterial factors in the expression of intercellular adhesion molecule-1 (ICAM-1) on human respiratory epithelial cells was investigated in response to B. pertussis. Flow cytometry and real time RT-PCR analysis showed that BEAS-2B human bronchial epithelial cells expressed increased levels of ICAM-1 mRNA and surface protein in response to B. pertussis infection. Filamentous hemagglutinin (FHA) played a role in this response because of the impaired capability of a FHA-deficient isogenic strain. A mutant strain in which an Arg-Gly-Asp (RGD) site of FHA had been changed to Arg-Ala-Asp had diminished ability to up-regulate ICAM-1 expression. RGD sequence-associated up-regulation of ICAM-1 expression was also observed in primary normal human bronchial epithelial cells. Pretreatment of cells with integrin antagonists such as RGD-containing peptide and antibody against very late antigen-5 (VLA-5) inhibited the up-regulation of ICAM-1 expression, suggesting the participation of VLA-5 integrin in this response. Pertussis toxin (PT) prevented the up-regulation of ICAM-1 expression because a PT-deficient mutant strain induced higher levels of ICAM-1 mRNA and surface protein than the parental strain. Consistent with this, purified PT suppressed the up-regulation of epithelial ICAM-1 expression. These findings demonstrate that B. pertussis FHA up-regulates ICAM-1 expression on respiratory epithelial cells through interaction of its RGD site with host cell VLA-5 integrin, and that PT impairs this response.

  12. Effects of 17 β-estradiol on lipopolysacharride-induced intracellular adhesion molecule-1 mRNA expression and Ca2+ homeostasis alteration in human endothelial cells

    PubMed Central

    Thor, Der; Zhang, Rui; Anderson, Leigh; Bose, Diptiman; Dubé, Gregory P.; Rahimian, Roshanak

    2010-01-01

    Recent evidence showed that 17 β-estradiol (E2) decreased cytokine-induced expression of cell adhesion molecules (CAM). Changes in intracellular Ca2+ concentration ([Ca2+]i) has been shown to be associated with CAM expression in endothelial cells. Here, the effects of E2 (1 μM, 24 h) on the expression of intracellular adhesion molecule-1 (ICAM-1) and [Ca2+]i were investigated in a lipopolysaccharide (LPS) (100 ng/mL, 18 h)-stimulated human endothelial cell line, EA.hy926, using real-time PCR and spectrofluorometry, respectively. PCR analysis revealed a significant increase in ICAM-1 expression in calcium ionophore A23187 (1 nM)- or LPS-stimulated cells. Pretreatment of cells with E2 significantly inhibited LPS-induced ICAM-1 mRNA expression. [Ca2+]i was monitored in Fura-2 AM-loaded cells in the presence and absence of extracellular Ca2+ with thapsigargin (TG, 1 μM), a sarco/endoplasmic reticulum ATPase inhibitor or ATP (100 μM). The extent of TG- or ATP-induced [Ca2+]i increase was significantly higher in LPS-stimulated cells than in control cells. Pre-treatment of LPS-stimulated cells with E2 limited the Ca2+ response to the same level as in control cells. Furthermore, ICI 182,780, an estrogen receptor antagonist, attenuated the inhibitory actions of E2 on ICAM-1 mRNA expression and Ca2+ responses, suggesting that estrogen receptors mediate, at least in part, the effects of estrogen. These data suggest a potential underlying mechanism for the protective effect of E2 against atherosclerosis. PMID:20843480

  13. Mesothelium expression of vascular cell adhesion molecule-1 (VCAM-1) is associated with an unfavorable prognosis in epithelial ovarian cancer (EOC).

    PubMed

    Scalici, Jennifer M; Arapovic, Sanja; Saks, Erin J; Atkins, Kristen A; Petroni, Gina; Duska, Linda R; Slack-Davis, Jill K

    2017-05-15

    Mesothelium vascular cell adhesion molecule-1 (VCAM-1) expression in the metastatic epithelial ovarian cancer (EOC) microenvironment is induced by tumor and mediates tumor cell invasion. VCAM-1 imaging suggests expression during treatment is an indicator of platinum resistance. Here, we assess the potential prognostic significance of mesothelium VCAM-1 expression and prospectively evaluate whether soluble VCAM-1 (sVCAM-1) is a surrogate for mesothelium expression. A retrospective review of EOC patients was performed to evaluate outcomes with mesothelium VCAM-1 expression determined by immunohistochemistry of peritoneum or omentum specimens. A prospective cohort of EOC patients was identified and followed through primary treatment. Serum for sVCAM-1 evaluation, which was performed via enzyme-linked immunosorbent assay, was collected before surgery or neoadjuvant chemotherapy and at each treatment cycle. Peritoneal specimens were obtained during debulking to assess mesothelial VCAM-1 expression. A retrospective review identified 54 advanced-stage EOC patients. Patients expressing mesothelium VCAM-1 had shortened overall survival (44 vs 79 months, P = 0.035) and progression-free survival (18 vs 67 months, P = 0.010); the median time to platinum resistance was 36 months for VCAM-1-expressing patients and not yet determined for the VCAM-1-negative group. In our prospective observational cohort, 18 EOC patients completed primary treatment; 3 were negative for mesothelium VCAM-1 expression, and sVCAM-1 did not vary between groups. Mesothelium VCAM-1 expression is negatively associated with progression-free and overall survival in EOC. This is especially compelling in light of previous data suggesting that persistent VCAM-1 expression during treatment is an indicator of platinum resistance. Our pilot study had insufficient cases to determine whether sVCAM-1 would substitute for mesothelium expression. Cancer 2017;123:977-84. © 2016 American Cancer Society. © 2016

  14. Testosterone attenuates expression of vascular cell adhesion molecule-1 by conversion to estradiol by aromatase in endothelial cells: implications in atherosclerosis.

    PubMed

    Mukherjee, Tapan K; Dinh, Hillary; Chaudhuri, Gautam; Nathan, Lauren

    2002-03-19

    We previously reported that testosterone attenuated atherogenesis in LDLR(-/-) male mice, and that this effect of testosterone was most likely caused by its conversion to estradiol. Estradiol inhibits vascular cell adhesion molecule-1 (VCAM-1) expression, and expression of VCAM-1 is one of the early events in atherogenesis. We assessed the cellular mechanism(s) involved by which testosterone attenuates atherogenesis. We evaluated whether testosterone inhibited TNFalpha-induced VCAM-1 expression via its conversion to estradiol by the enzyme aromatase in human umbilical vein endothelial cells (HUVEC). Aromatase mRNA was dedected by reverse transcription-PCR in these cells. Testosterone (30 nM-1 microM) attenuated VCAM-1 mRNA expression in a concentration-dependent manner. The non aromatizable androgen, dihydrotestosterone, had no effect on VCAM-1 mRNA expression. Testosterone was less effective in attenuating VCAM-1 expression in the presence of anastrozole, an inhibitor of aromatase, indicating that testosterone inhibited VCAM-1 via conversion to estradiol. Estradiol also attenuated VCAM-1 mRNA expression, but this action was not abolished in the presence of anastrozole, indicating that anastrozole itself did not modulate VCAM-1 mRNA expression. The effect of testosterone on VCAM-1 mRNA expression was inhibited in the presence of the estrogen receptor antagonist, ICI-182780. Testosterone also attenuated TNFalpha-induced VCAM-1 protein expression, and this attenuation was abolished in the presence of anastrozole. In conclusion, testosterone inhibited VCAM-1 mRNA and protein expression in HUVEC by its conversion to estradiol via the enzyme aromatase present in the endothelial cells. Results from our study may help explain the mechanism by which testosterone may have beneficial effects on the cardiovascular system.

  15. Expression of 7F7-antigen, a human adhesion molecule identical to intercellular adhesion molecule-1 (ICAM-1) in human carcinomas and their stromal fibroblasts.

    PubMed

    Vogetseder, W; Feichtinger, H; Schulz, T F; Schwaeble, W; Tabaczewski, P; Mitterer, M; Böck, G; Marth, C; Dapunt, O; Mikuz, G

    1989-05-15

    The 7F7-antigen is a widespread 85-kDa membrane adherence molecule involved in heterotypic adhesion between PHA-blasts and fibroblasts. Immunofluorescence analysis of COS cells transfected with clone pICAM-I indicated that 7F7-antigen is identical with ICAM-I, the ligand for the contact molecule LFA-I. We have investigated the expression of ICAM-I on several human carcinomas. Tumor cells in most carcinomas, with the exception of squamous-cell carcinomas, expressed very little ICAM-I or none at all. In contrast, marked expression of this molecule was observed on fibrous tissue in the vicinity of carcinoma cells, its intensity correlating with lymphatic infiltration in these tumors. We also examined the expression of ICAM-I on carcinoma cell lines and its induction by treatment with interferon-gamma (IFN-gamma). The inducibility of ICAM-I expression on cultured fibroblasts by several lymphokines suggests that the expression of ICAM-I in the vicinity of carcinoma cells is effected by lymphokines produced by activated lymphocytes/macrophages within the tumor.

  16. Interleukin-6 and intercellular cell adhesion molecule-1 expression remains elevated in revived live endothelial cells following spaceflight.

    PubMed

    Muid, S; Froemming, G R A; Ali, A M; Nawawi, H

    2013-12-01

    The effects of spaceflight on cardiovascular health are not necessarily seen immediately after astronauts have returned but can be delayed. It is important to investigate the long term effects of spaceflight on protein and gene expression of inflammation and endothelial activation as a predictor for the development of atherosclerosis and potential cardiovascular problems. The objectives of this study were to investigate the (a) protein and gene expression of inflammation and endothelial activation, (b) expression of nuclear factor kappa B (NFκB), signal transducer and activator of transcription-3 (STAT-3) and endothelial nitric oxide synthase (eNOS) in human umbilical vein endothelial cells (HUVEC) 3 months post-space flight travel compared to ground controls. HUVEC cultured on microcarriers in fluid processing apparatus were flown to the International Space Station (ISS) by the Soyuz TMA-11 rocket. After landing, the cells were detached from microcarriers and recultured in T-25 cm(2) culture flasks (Revived HUVEC). Soluble protein expression of IL-6, TNF-α, ICAM-1, VCAM-1 and e-selectin were measured by ELISA. Gene expression of these markers and in addition NFκB, STAT-3 and eNOS were measured. Spaceflight induced IL-6 and ICAM-1 remain elevated even after 3 months post spaceflight travel and this is mediated via STAT-3 pathway. The downregulation of eNOS expression in revived HUVEC cells suggests a reduced protection of the cells and the surrounding vessels against future insults that may lead to atherosclerosis. It would be crucial to explore preventive measures, in relation to atherosclerosis and its related complications.

  17. Minodronate, a nitrogen-containing bisphosphonate, inhibits advanced glycation end product-induced vascular cell adhesion molecule-1 expression in endothelial cells by suppressing reactive oxygen species generation.

    PubMed

    Yamagishi, S; Matsui, T; Nakamura, K; Takeuchi, M

    2005-01-01

    Advanced glycation end products (AGEs), the senescent macroprotein derivatives that form in increased amounts in diabetes, have been implicated in the pathogenesis of diabetic vascular complications. Indeed, AGEs elicit oxidative stress generation in vascular wall cells through an interaction with their receptor (RAGE), thus playing an important role in vascular inflammation and altered gene expression of growth factors and cytokines. We have previously shown that minodronate, a nitrogen-containing bisphosphonate, blocked the angiogenic signaling of vascular endothelial growth factor in ECs through its antioxidative properties. However, the effects of minodronate on AGE-exposed ECs remain to be elucidated. In this study, we investigated whether and how minodronate could inhibit AGE-induced reactive oxygen species (ROS) generation and subsequent vascular cell adhesion molecule-1 (VCAM-1) gene expression in human umbilical vein endothelial cells (HUVEC). Minodronate or an NADPH oxidase inhibitor, diphenylene iodonium, completely inhibited the AGE-induced ROS generation in HUVEC. Geranylgeranyl pyrophosphate reversed the antioxidative properties of minodronate in AGE-exposed ECs. Furthermore, minodronate was found to prevent AGE-induced nuclear factor--KB activation and subsequently suppress VCAM-1 gene expression in HUVEC. These results demonstrate that minodronate could inhibit VCAM- 1 expression in AGE-exposed ECs by suppressing NADPH oxidase-derived ROS generation, probably via inhibition of geranylgeranylation of Rac, a component of endothelial NADPH oxidase. Our present study suggests that minodronate may have a therapeutic potential in the treatment of patients with diabetic vascular complications.

  18. Neopterin-induced expression of intercellular adhesion molecule-1 (ICAM-1) in type II-like alveolar epithelial cells

    PubMed Central

    Hoffmann, G; Rieder, J; Smolny, M; Seibel, M; Wirleitner, B; Fuchs, D; Schobersberger, W

    1999-01-01

    Production and release of proinflammatory mediators such as tumour necrosis factor-alpha and neopterin are common events following the activation of the cellular immune system. Concerning inflammatory disorders of the lung, e.g. sepsis or sarcoidosis, high serum neopterin levels have been reported to correlate well with the severity of the disease. These situations are often associated with an increased expression of ICAM-1 reported to be induced in type II alveolar epithelial cells. In our study we investigated the potential effects of neopterin on ICAM-1 synthesis in the type II-like pneumocyte cell line L2. Detection of ICAM-1 gene expression by reverse transcriptase-polymerase chain reaction revealed a dose-dependent effect of neopterin, with maximum impact following 12-h incubations. Comparable results were obtained when ICAM-1 protein synthesis was measured via a cell-based ELISA. In a second set of experiments we were able to show that coincubation of L2 cells with pyrrolidine dithiocarbamate (PDTC) significantly suppressed neopterin-induced ICAM-1 synthesis. Since PDTC is known to be a potent inhibitor of NF-κB, the stimulating effects of neopterin on ICAM-1 gene expression and protein generation may be mediated by activation of this transcription factor. From these data we conclude that neopterin stimulates ICAM-1 production in L2 cells. In vivo, these effects may contribute to the prolongation of the inflammatory response, including cytotoxic cell host defence mechanisms that impair the functions of the airway epithelium. PMID:10594564

  19. Activation of transcription factor AP-2 mediates UVA radiation- and singlet oxygen-induced expression of the human intercellular adhesion molecule 1 gene

    SciTech Connect

    Grether-Beck, S.; Olaizola-Horn, S.; Schmitt, H.; Grewe, M.

    1996-12-10

    UVA radiation is the major component of the UV solar spectrum that reaches the earth, and the therapeutic application of UVA radiation is increasing in medicine. Analysis of the cellular effects of UVA radiation has revealed that exposure of human cells to UVA radiation at physiological doses leads to increased gene expression and that this UVA response is primarily mediated through the generation of singlet oxygen. In this study, the mechanisms by which UVA radiation induces transcriptional activation of the human intercellular adhesion molecule 1 (ICAM-1) were examined. UVA radiation was capable of inducing activation of the human ICAM-1 promoter and increasing OCAM-1 mRNA and protein expression. These UVA radiation effects were inhibited by singlet oxygen quenchers, augmented by enhancement of singlet oxygen life-time, and mimicked in unirradiated cells by a singlet oxygen-generating system. UVA radiation as well as singlet oxygen-induced ICAM-1 promoter activation required activation of the transcription factor AP-2. Accordingly, both stimuli activated AP-2, and deletion of the putative AP-2-binding site abrogated ICAM-1 promoter activation in this system. This study identified the AP-2 site as the UVA radiation- and singlet oxygen-responsive element of the human ICAM-1 gene. The capacity of UVA radiation and/or singlet oxygen to induce human gene expression through activation of AP-2 indicates a previously unrecognized role of this transcription factor in the mammalian stress response. 38 refs., 3 figs., 3 tabs.

  20. Cell adhesion molecule-1 (CADM1) expressed on adult T-cell leukemia/lymphoma cells is not involved in the interaction with macrophages.

    PubMed

    Komohara, Yoshihiro; Ma, Chaoya; Yano, Hiromu; Pan, Cheng; Horlad, Hasita; Saito, Yoichi; Ohnishi, Koji; Fujiwara, Yukio; Okuno, Yutaka; Nosaka, Kisato; Shimosaki, Shunsuke; Morishita, Kazuhiro; Matsuoka, Masao; Wakayama, Tomohiko; Takeya, Motohiro

    2017-07-05

    Cell adhesion molecule 1 (CADM1) is a cell adhesion molecule that is expressed in brain, liver, lung, testis, and some kinds of cancer cells including adult T-cell leukemia/lymphoma (ATLL). Recent studies have indicated the involvement of CADM1 in cell-cell contact between cytotoxic T-lymphocytes and virus infected cells. We previously reported that cell-cell interaction between lymphoma cells and macrophages induces lymphoma cell proliferation. In the present study, we investigated whether CADM1 is associated with cell-cell interaction between several human lymphoma cell lines and macrophages.CADM1 expression was observed in the ATLL cell lines, ATN-1, ATL-T, and ATL-35T, and in the B cell lymphoma cell lines, TL-1, DAUDI, and SLVL, using western blotting. Significant cell-cell interaction between macrophages and ATN-1, ATL-T, ATL-35T and MT-2, DAUDI, and SLVL cells, as assessed by induction of cell proliferation, was observed. Immunohistochemical analysis of human biopsy samples indicated CADM1 expression in 10 of 14 ATLL cases; however, no case of follicular lymphoma or diffuse large B-cell lymphoma was positive for CADM1. Finally, the interaction of macrophages with cells of the CADM1-negative ED ATLL cell line and CADM1-transfected ED cells was tested. However, significant cell-cell interaction between macrophage and CADM1-transfected ED cells was not observed. We conclude that CADM1 was not associated with cell-cell interaction between lymphoma cells and macrophages, although CADM1 may be a useful marker of ATLL for diagnostic procedures.

  1. 5-Hydroxymethylfurfural from black garlic extract prevents TNFα-induced monocytic cell adhesion to HUVECs by suppression of vascular cell adhesion molecule-1 expression, reactive oxygen species generation and NF-κB activation.

    PubMed

    Kim, Hye Kyung; Choi, Young-Whan; Lee, Eun Na; Park, Jin Kyeong; Kim, Sun-Gun; Park, Da-Jung; Kim, Bong-Seon; Lim, Young-Tak; Yoon, Sik

    2011-07-01

    5-Hydroxymethylfurfural (5-HMF) is a common Maillard reaction product; the reaction occurs during heat-processing and the preparation of many types of foods and beverages. Although 5-HMF has been proposed to have harmful effects, recently, its beneficial effects, including antioxidant, cytoprotective and antitumor effects have become increasingly apparent. It was found recently that a chloroform extract of aged black garlic shows antiinflammatory properties when administered to human umbilical vein endothelial cells (HUVECs). This study investigated the antiinflammatory potential of 5-HMF purified from the chloroform extract of aged black garlic in tumor necrosis factor-α (TNF-α)-stimulated HUVECs. Treatment of HUVECs with 5-HMF strongly suppressed TNF-α-induced cell surface and total protein expression of vascular cell adhesion molecule-1 (VCAM-1) and intercellular cell adhesion molecule-1 (ICAM-1) as well as their mRNA expression. In addition, 5-HMF significantly inhibited TNF-α-induced reactive oxygen species formation, and markedly reduced THP-1 monocyte adhesion to TNF-α-stimulated HUVECs. Furthermore, 5-HMF significantly inhibited NF-κB transcription factor activation in TNF-α-stimulated HUVECs. The data provide new evidence of the antiinflammatory properties of 5-HMF in support of its potential therapeutic use for the prevention and management of vascular diseases such as atherosclerosis through mechanisms involving the inhibition of VCAM-1 expression and NF-κB activation in vascular endothelial cells. Copyright © 2011 John Wiley & Sons, Ltd.

  2. Prostaglandin E₂-induced intercellular adhesion molecule-1 expression is mediated by cAMP/Epac signalling modules in bEnd.3 brain endothelial cells.

    PubMed

    Park, Tae Yeop; Baik, Eun Joo; Lee, Soo Hwan

    2013-06-01

    Prostaglandin E₂ (PGE₂) has been implicated in the regulation of adhesion molecules, leukocyte adhesion and infiltration into inflamed site. However, the underlying mechanism therein involved remains ill-defined. In this study, we explored its cellular mechanism of action in the regulation of the intercellular adhesion molecule-1 (ICAM-1) expression in the brain endothelial cells. bEnd.3 cells, the murine cerebrovascular endothelial cell line and primary mouse brain endothelial cells were treated with PGE₂ with or without agonists/antagonists of PGE₂ receptors and associated signalling molecules. ICAM-1 expression, Akt phosphorylation and activity of NF-κB were determined by reverse transcription polymerase chain reaction (RT-PCR), immunoblot analysis, luciferase assay and immunocytochemistry. PGE₂ significantly up-regulated the expression of ICAM-1, which was blocked by EP4 antagonist (ONO-AE2-227) and knock-down of EP4. PGE₂ effects were mimicked by forskolin, dibutyryl cAMP (dbcAMP) and an exchange protein directly activated by cAMP (Epac) activator (8-Cpt-cAMP) but not a protein kinase A activator (N⁶-Bnz-cAMP). PGE₂-induced ICAM-1 expression was reduced by knock-down of Epac1. A PI3K specific inhibitor (LY294002), Akt inhibitor VIII (Akti) and NF-κB inhibitors (Bay-11-7082 and MG-132) attenuated the induction of ICAM-1 by PGE₂. PGE₂, dbcAMP and 8-Cpt-cAMP induced the phosphorylation of Akt, IκB kinase and IκBα and the translocation of p65 to the nucleus and increased NF-κB dependent reporter gene activity, which was diminished by Akti. Our findings suggest that PGE₂ induces ICAM-1 expression via EP4 receptor and Epac/Akt/NF-κB signalling pathway in bEnd.3 brain endothelial cells, supporting its pathophysiological role in brain inflammation. © 2013 The Authors. British Journal of Pharmacology © 2013 The British Pharmacological Society.

  3. Prostaglandin E2-induced intercellular adhesion molecule-1 expression is mediated by cAMP/Epac signalling modules in bEnd.3 brain endothelial cells

    PubMed Central

    Park, Tae Yeop; Baik, Eun Joo; Lee, Soo Hwan

    2013-01-01

    Background and Purpose Prostaglandin E2 (PGE2) has been implicated in the regulation of adhesion molecules, leukocyte adhesion and infiltration into inflamed site. However, the underlying mechanism therein involved remains ill-defined. In this study, we explored its cellular mechanism of action in the regulation of the intercellular adhesion molecule-1 (ICAM-1) expression in the brain endothelial cells. Experimental Approach bEnd.3 cells, the murine cerebrovascular endothelial cell line and primary mouse brain endothelial cells were treated with PGE2 with or without agonists/antagonists of PGE2 receptors and associated signalling molecules. ICAM-1 expression, Akt phosphorylation and activity of NF-κB were determined by reverse transcription polymerase chain reaction (RT-PCR), immunoblot analysis, luciferase assay and immunocytochemistry. Key Results PGE2 significantly up-regulated the expression of ICAM-1, which was blocked by EP4 antagonist (ONO-AE2-227) and knock-down of EP4. PGE2 effects were mimicked by forskolin, dibutyryl cAMP (dbcAMP) and an exchange protein directly activated by cAMP (Epac) activator (8-Cpt-cAMP) but not a protein kinase A activator (N6-Bnz-cAMP). PGE2-induced ICAM-1 expression was reduced by knock-down of Epac1. A PI3K specific inhibitor (LY294002), Akt inhibitor VIII (Akti) and NF-κB inhibitors (Bay-11–7082 and MG-132) attenuated the induction of ICAM-1 by PGE2. PGE2, dbcAMP and 8-Cpt-cAMP induced the phosphorylation of Akt, IκB kinase and IκBα and the translocation of p65 to the nucleus and increased NF-κB dependent reporter gene activity, which was diminished by Akti. Conclusion and Implications Our findings suggest that PGE2 induces ICAM-1 expression via EP4 receptor and Epac/Akt/NF-κB signalling pathway in bEnd.3 brain endothelial cells, supporting its pathophysiological role in brain inflammation. PMID:23317035

  4. P2Y2 nucleotide receptor activation up-regulates vascular cell adhesion molecule-1 [corrected] expression and enhances lymphocyte adherence to a human submandibular gland cell line.

    PubMed

    Baker, Olga J; Camden, Jean M; Rome, Danny E; Seye, Cheikh I; Weisman, Gary A

    2008-01-01

    Sjögren's syndrome (SS) is a chronic inflammatory autoimmune disease that causes salivary and lacrimal gland tissue destruction resulting in impaired secretory function. Although lymphocytic infiltration of salivary epithelium is associated with SS, the mechanisms involved have not been adequately elucidated. Our previous studies have shown that the G protein-coupled P2Y2 nucleotide receptor (P2Y2R) is up-regulated in response to damage or stress of salivary gland epithelium, and in salivary glands of the NOD.B10 mouse model of SS-like autoimmune exocrinopathy. Additionally, we have shown that P2Y2R activation up-regulates vascular cell adhesion molecule-1 (VCAM-1) expression in endothelial cells leading to the binding of monocytes. The present study demonstrates that activation of the P2Y2R in dispersed cell aggregates from rat submandibular gland (SMG) and in human submandibular gland ductal cells (HSG) up-regulates the expression of VCAM-1. Furthermore, P2Y2R activation mediated the up-regulation of VCAM-1 expression in HSG cells leading to increased adherence of lymphocytic cells. Inhibitors of EGFR phosphorylation and metalloprotease activity abolished P2Y2R-mediated VCAM-1 expression and decreased lymphocyte binding to HSG cells. Moreover, silencing of EGFR expression abolished UTP-induced VCAM-1 up-regulation in HSG cells. These results suggest that P2Y2R activation in salivary gland cells increases the EGFR-dependent expression of VCAM-1 and the binding of lymphocytes, a pathway relevant to inflammation associated with SS.

  5. Expression of various MHC class II molecules and of intracellular adhesion molecule-1 (ICAM-1) on focal clusters of dendritic cells in iodine deficiency goitres

    PubMed Central

    Dimal, P.; Wilders-Truschnig, M.; Mooij, P.; Leb, G.; Eber, O.; Langsteger, W.; Hebenstreit, J.; Beham, A.; Stiegler, C.; Dohr, G.; Drexhage, H. A.

    1993-01-01

    Thyroid sections from 18 consecutive euthyroid patients undergoing surgery for iodine deficiency goitre were investigated by means of immunohistochemistry and immunofluorescence, evaluating the expression of MHC class II antigens (HLA-DR, -DP, -DQ, and RFD1) and intercellular adhesion molecule-1 on the formerly described clusters of dendritic cells, as well as on thyrocytes. Eleven of 18 iodine deficiency goitres contained clusters of dendritic cells. These clusters appeared to express only HLA-DR in two cases; in nine of 12 cases they showed a differential expression of class II molecules in the following frequency: HLA-DR>DQ and/or -DP>RFD1. These dendritic cells also were ICAM-1+. In four of 18 iodine deficiency goitres, thyroid epithelial cells showed MHC class II expression in several combinations, but were ICAM-1-. In normal thyroids and in nodular goitres from inhabitants of the endemic area not having an actual iodine deficiency, only sparse clusters of dendritic cells were found; these cells were only HLA-DR+. Follicle lining cells were negative for the MHC class II molecules. In normal thyroids from an area with sufficient iodine supply, no clusters of dendritic cells were seen. The few dendritic cells observed were lying isolated in the interstitium and only positive for HLA-DR and ICAM-1; epithelial cells were negative for the studied markers. These data show clusters of dendritic cells in thyroids of inhabitants of an endemic area. When goitre is accompanied by iodine deficiency at the moment of operation, there appears to be activation of these dendritic cells and of thyroid epithelial cells. ImagesFig. 1Fig. 2 PMID:8099855

  6. Effects of aqueous extracts of Taraxacum Officinale on expression of tumor necrosis factor-alpha and intracellular adhesion molecule 1 in LPS-stimulated RMMVECs.

    PubMed

    Hu, Ge; Wang, Junjie; Hong, Dong; Zhang, Tao; Duan, Huiqin; Mu, Xiang; Yang, Zuojun

    2017-01-11

    Mastitis gives rise to big financial burden to farm industry (mainly dairy production) and public health. Its incidence is currently high and therefore, highly effective treatments for therapy, especially with natural products are required. Taraxacum officinale has been reported to use for anti-inflammation. However, its effect on endothelium during mastitis has not been reported. We firstly established inflammation experimental model of rat mammary microvascular endothelial cells (RMMVECs). We evaluated the effects of dandelion leaf aqueous extracts (DAE) on LPS-induced production of inflammatory mediators in RMMVECs by enzyme-linked immunosorbent assay and Western blot. We treated RMMVECs with 1 μg/ml LPS for 4 h and then incubated with 10, 100 and 200 μg/mL DAE for 4, 8, 12 and 24 h. The expression (mRNA and protein level) of targets (tumor necrosis factor-alpha (TNF- α) and Intracellular Adhesion Molecule 1 (ICAM1) was analyzed by employing real-time PCR and Western blots. The in vivo anti-inflammatory effect of DAE on mastitis within an Staphylococcus aureus-induced mouse model was also determined. The obtained results showed that dandelion extracts at the concentration of 100 and 200 μg/mL could significantly inhibit both TNF-α and ICAM-1 expression in all time points checked while 10 μg/mL of dandelion only suppress both expression at 8 and 12 h post-treatment. The in vivo tests showed that the DAE inhibited the expression of TNF-α and ICAM-1 in a time-dependent manner. All results suggest that the endothelium may use as as a possible target of dandelion for anti-inflammation.

  7. Glucocorticoid-induced tumor necrosis factor receptor family-related ligand triggering upregulates vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 and promotes leukocyte adhesion.

    PubMed

    Lacal, Pedro Miguel; Petrillo, Maria Grazia; Ruffini, Federica; Muzi, Alessia; Bianchini, Rodolfo; Ronchetti, Simona; Migliorati, Graziella; Riccardi, Carlo; Graziani, Grazia; Nocentini, Giuseppe

    2013-10-01

    The interaction of glucocorticoid-induced tumor necrosis factor receptor-family related (GITR) protein with its ligand (GITRL) modulates different functions, including immune/inflammatory response. These effects are consequent to intracellular signals activated by both GITR and GITRL. Previous results have suggested that lack of GITR expression in GITR(-/-) mice decreases the number of leukocytes within inflamed tissues. We performed experiments to analyze whether the GITRL/GITR system modulates leukocyte adhesion and extravasation. For that purpose, we first evaluated the capability of murine splenocytes to adhere to endothelial cells (EC). Our results indicated that adhesion of GITR(-/-) splenocytes to EC was reduced as compared with wild-type cells, suggesting that GITR plays a role in adhesion and that this effect may be due to GITRL-GITR interaction. Moreover, adhesion was increased when EC were pretreated with an agonist GITR-Fc fusion protein, thus indicating that triggering of GITRL plays a role in adhesion by EC regulation. In a human in vitro model, the adhesion to human EC of HL-60 cells differentiated toward the monocytic lineage was increased by EC pretreatment with agonist GITR-Fc. Conversely, antagonistic anti-GITR and anti-GITRL Ab decreased adhesion, thus further indicating that GITRL triggering increases the EC capability to support leukocyte adhesion. EC treatment with GITR-Fc favored extravasation, as demonstrated by a transmigration assay. Notably, GITRL triggering increased intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) expression and anti-ICAM-1 and anti-VCAM-1 Abs reversed GITR-Fc effects. Our study demonstrates that GITRL triggering in EC increases leukocyte adhesion and transmigration, suggesting new anti-inflammatory therapeutic approaches based on inhibition of GITRL-GITR interaction.

  8. Maternal serum uric acid concentration is associated with the expression of tumour necrosis factor-α and intercellular adhesion molecule-1 in patients with preeclampsia.

    PubMed

    Zhao, J; Zheng, D-Y; Yang, J-M; Wang, M; Zhang, X-T; Sun, L; Yun, X-G

    2016-07-01

    We aimed to investigate whether there is a correlation between elevated serum uric acid (SUA) concentration and endothelial inflammatory response in women with preeclampsia (PE). On the basis of clinical and laboratory findings, patients were assigned to three groups: normal blood pressure (Control (Con)), gestational hypertension (GH) and PE (n=50 in each group). SUA concentration was measured by spectrophotometry, and serum tumour necrosis factor-α (TNF-α) and intercellular adhesion molecule-1 (ICAM-1) levels were measured by enzyme-linked immunosorbent assay. Western blotting and immunohistochemical staining were also used to detect the changes in TNF-α and ICAM-1 expression in subcutaneous fat tissue. PE patients showed significantly higher systolic and diastolic blood pressures compared with Con and GH pregnant women (P=0.02 and P=0.02, respectively). The changes of body mass index (ΔBMI) before and after pregnancy and 24-h urine protein were significantly different among the three groups (P<0.001). Maternal SUA, TNF-α and soluble ICAM-1 (sICAM-1) levels were significantly increased in the patients with PE (P<0.05) compared with the other two groups. Scatterplot analysis revealed that elevated SUA concentration positively correlated with TNF-α and sICAM-1 in pregnant women. Moreover, vessels in subcutaneous fat tissues of preeclamptic patients showed intense TNF-α and ICAM-1 staining compared with Con and GH patients. The results support that, to a certain extent, elevated SUA concentration is significantly associated with inflammation of maternal systemic vasculature as indicated by increased TNF-α and ICAM-1 expression in women with PE.

  9. Human peripheral blood eosinophils express a functional c-kit receptor for stem cell factor that stimulates very late antigen 4 (VLA-4)-mediated cell adhesion to fibronectin and vascular cell adhesion molecule 1 (VCAM-1).

    PubMed

    Yuan, Q; Austen, K F; Friend, D S; Heidtman, M; Boyce, J A

    1997-07-21

    We evaluated mature peripheral blood eosinophils for their expression of the surface tyrosine kinase, c-kit, the receptor for the stromal cell-derived cytokine, stem cell factor (SCF). Cytofluorographic analysis revealed that c-kit was expressed on the purified peripheral blood eosinophils from 8 of 8 donors (4 nonatopic and 4 atopic) (mean channel fluorescence intensity 2.0- 3. 6-fold, average 2.8 +/- 0.6-fold, greater than the negative control). The uniform and selective expression of c-kit by eosinophils was confirmed by immunohistochemical analysis of peripheral blood buffy coats. The functional integrity of c-kit was demonstrated by the capacity of 100 ng/ml (5 nM) of recombinant human (rh) SCF to increase eosinophil adhesion to 3, 10, and 30 microg/ml of immobilized FN40, a 40-kD chymotryptic fragment of plasma fibronectin, in 15 min by 7.7 +/- 1.4-, 5.3 +/- 3.3-, and 5.4 +/- 0. 2-fold, respectively, and their adhesion to 0.1, 0.5, and 1.0 microg/ml vascular cell adhesion molecule-1 (VCAM-1), by 12.7 +/- 9. 2-, 3.8 +/- 2.5-, and 1.7 +/- 0.6-fold, respectively. The SCF-stimulated adhesion occurred without concomitant changes in surface integrin expression, thereby indicating an avidity-based mechanism. rhSCF (100 ng/ml, 5 nM) was comparable to rh eotaxin (200 ng/ml, 24 nM) in stimulating adhesion. Cell adhesion to FN40 was completely inhibited with antibodies against the alpha4 and beta1 integrin subunits, revealing that the SCF/c-kit adhesion effect was mediated by a single integrin heterodimer, very late antigen 4 (VLA-4). Thus, SCF represents a newly recognized stromal ligand for the activation of eosinophils for VLA-4-mediated adhesion, which could contribute to the exit of these cells from the blood, their tissue localization, and their prominence in inflammatory lesions.

  10. Human Peripheral Blood Eosinophils Express a Functional c-kit Receptor for Stem Cell Factor that Stimulates Very Late Antigen 4 (VLA-4)–mediated Cell Adhesion to Fibronectin and Vascular Cell Adhesion Molecule 1 (VCAM-1)

    PubMed Central

    Yuan, Qian; Austen, K. Frank; Friend, Daniel S.; Heidtman, Matthew; Boyce, Joshua A.

    1997-01-01

    We evaluated mature peripheral blood eosinophils for their expression of the surface tyrosine kinase, c-kit, the receptor for the stromal cell–derived cytokine, stem cell factor (SCF). Cytofluorographic analysis revealed that c-kit was expressed on the purified peripheral blood eosinophils from 8 of 8 donors (4 nonatopic and 4 atopic) (mean channel fluorescence intensity 2.0– 3.6-fold, average 2.8 ± 0.6-fold, greater than the negative control). The uniform and selective expression of c-kit by eosinophils was confirmed by immunohistochemical analysis of peripheral blood buffy coats. The functional integrity of c-kit was demonstrated by the capacity of 100 ng/ml (5 nM) of recombinant human (rh) SCF to increase eosinophil adhesion to 3, 10, and 30 μg/ml of immobilized FN40, a 40-kD chymotryptic fragment of plasma fibronectin, in 15 min by 7.7 ± 1.4-, 5.3 ± 3.3-, and 5.4 ± 0.2-fold, respectively, and their adhesion to 0.1, 0.5, and 1.0 μg/ml vascular cell adhesion molecule-1 (VCAM-1), by 12.7 ± 9.2-, 3.8 ± 2.5-, and 1.7 ± 0.6-fold, respectively. The SCF-stimulated adhesion occurred without concomitant changes in surface integrin expression, thereby indicating an avidity-based mechanism. rhSCF (100 ng/ml, 5 nM) was comparable to rh eotaxin (200 ng/ml, 24 nM) in stimulating adhesion. Cell adhesion to FN40 was completely inhibited with antibodies against the α4 and β1 integrin subunits, revealing that the SCF/c-kit adhesion effect was mediated by a single integrin heterodimer, very late antigen 4 (VLA-4). Thus, SCF represents a newly recognized stromal ligand for the activation of eosinophils for VLA-4–mediated adhesion, which could contribute to the exit of these cells from the blood, their tissue localization, and their prominence in inflammatory lesions. PMID:9221761

  11. Intercellular Adhesion Molecule 1 Knockout Abrogates Radiation Induced Pulmonary Inflammation

    NASA Astrophysics Data System (ADS)

    Hallahan, Dennis E.; Virudachalam, Subbulakshmi

    1997-06-01

    Increased expression of intercellular adhesion molecule 1 (ICAM-1; CD54) is induced by exposure to ionizing radiation. The lung was used as a model to study the role of ICAM-1 in the pathogenesis of the radiation-induced inflammation-like response. ICAM-1 expression increased in the pulmonary microvascular endothelium and not in the endothelium of larger pulmonary vessels following treatment of mice with thoracic irradiation. To quantify radiation-induced ICAM-1 expression, we utilized fluorescence-activated cell sorting analysis of anti-ICAM-1 antibody labeling of pulmonary microvascular endothelial cells from human cadaver donors (HMVEC-L cells). Fluorochrome conjugates and UV microscopy were used to quantify the fluorescence intensity of ICAM in the irradiated lung. These studies showed a dose- and time-dependent increase in ICAM-1 expression in the pulmonary microvascular endothelium. Peak expression occurred at 24 h, while threshold dose was as low as 2 Gy. To determine whether ICAM-1 is required for inflammatory cell infiltration into the irradiated lung, the anti-ICAM-1 blocking antibody was administered by tail vein injection to mice following thoracic irradiation. Inflammatory cells were quantified by immunofluorescence for leukocyte common antigen (CD45). Mice treated with the anti-ICAM-1 blocking antibody showed attenuation of inflammatory cell infiltration into the lung in response to ionizing radiation exposure. To verify the requirement of ICAM-1 in the inflammation-like radiation response, we utilized the ICAM-1 knockout mouse. ICAM-1 was not expressed in the lungs of ICAM-1-deficient mice following treatment with thoracic irradiation. ICAM-1 knockout mice had no increase in the inflammatory cell infiltration into the lung in response to thoracic irradiation. These studies demonstrate a radiation dose-dependent increase in ICAM-1 expression in the pulmonary microvascular endothelium, and show that ICAM-1 is required for inflammatory cell infiltration

  12. Ultraviolet radiation can either suppress or induce expression of intercellular adhesion molecule 1 (ICAM-1) on the surface of cultured human keratinocytes

    SciTech Connect

    Norris, D.A.; Lyons, M.B.; Middleton, M.H.; Yohn, J.J.; Kashihara-Sawami, M. )

    1990-08-01

    Interactions of the ligand/receptor pair LFA-1(CD11a/CD18) and ICAM-1(CD54) initiate and control the cell-cell interactions of leukocytes and interactions of leukocytes with parenchymal cells in all phases of the immune response. Induction of the intercellular adhesion molecule 1 (ICAM-1) on the surface of epidermal keratinocytes has been proposed as an important regulator of contact-dependent aspects of cutaneous inflammation. Ultraviolet radiation (UVR) also modifies cutaneous inflammation, producing both up- and down-regulation of contact hypersensitivity. We have found that UVR has a biphasic effect on the induction of keratinocyte CD54. Using immunofluorescence and FACS techniques to quantitate cell-surface CD54 staining, we have shown that UVR significantly (p less than 0.01) inhibits keratinocyte CD54 induction by gamma interferon 24 h after irradiation. However, at 48, 72, and 96 h after UVR, CD54 expression is significantly induced to levels even greater than are induced by gamma interferon (20 U/ml). In addition, at 48, 72, or 96 h following UVR (30-100 mJ/cm2), the gamma-interferon-induced CD54 expression on human keratinocytes is also strongly (p less than 0.05 to p less than 0.001) enhanced. In this cell-culture system, gamma interferon and TNF-alpha are both strong CD54 inducers and are synergistic, but GM-CSF, TFG-beta, and IL-1 have no direct CD54-inducing effects. Thus the effects of UVR on CD54 induction are biphasic, producing inhibition at 24 h and induction at 48, 72, and 96 h. This effect on CD54 may contribute to the biphasic effects of UVR on delayed hypersensitivity in vivo. The early inhibition of ICAM-1 by UVR may also contribute to the therapeutic effects of UVR. We also speculate that the late induction of ICAM-1 by UVR might be an important step in the induction of photosensitive diseases such as lupus erythematosus.

  13. Intercellular adhesion molecule-1 augments myoblast adhesion and fusion through homophilic trans-interactions.

    PubMed

    Pizza, Francis X; Martin, Ryan A; Springer, Evan M; Leffler, Maxwell S; Woelmer, Bryce R; Recker, Isaac J; Leaman, Douglas W

    2017-07-11

    The overall objective of the study was to identify mechanisms through which intercellular adhesion molecule-1 (ICAM-1) augments the adhesive and fusogenic properties of myogenic cells. Hypotheses were tested using cultured myoblasts and fibroblasts, which do not constitutively express ICAM-1, and myoblasts and fibroblasts forced to express full length ICAM-1 or a truncated form lacking the cytoplasmic domain of ICAM-1. ICAM-1 mediated myoblast adhesion and fusion were quantified using novel assays and cell mixing experiments. We report that ICAM-1 augments myoblast adhesion to myoblasts and myotubes through homophilic trans-interactions. Such adhesive interactions enhanced levels of active Rac in adherent and fusing myoblasts, as well as triggered lamellipodia, spreading, and fusion of myoblasts through the signaling function of the cytoplasmic domain of ICAM-1. Rac inhibition negated ICAM-1 mediated lamellipodia, spreading, and fusion of myoblasts. The fusogenic property of ICAM-1-ICAM-1 interactions was restricted to myogenic cells, as forced expression of ICAM-1 by fibroblasts did not augment their fusion to ICAM-1+ myoblasts/myotubes. We conclude that ICAM-1 augments myoblast adhesion and fusion through its ability to self-associate and initiate Rac-mediated remodeling of the actin cytoskeleton.

  14. The association between soluble intercellular adhesion molecule-1 levels in drained dialysate and peritoneal injury in peritoneal dialysis.

    PubMed

    Igarashi, Yusuke; Morishita, Yoshiyuki; Yoshizawa, Hiromichi; Imai, Reika; Imai, Toshimi; Hirahara, Ichiro; Akimoto, Tetsu; Ookawara, Susumu; Ishibashi, Kenichi; Muto, Shigeaki; Nagata, Daisuke

    2017-11-01

    Chronic inflammation of the peritoneum causes peritoneal injury in patients on peritoneal dialysis. Intercellular adhesion molecule-1 and its circulating form, soluble intercellular adhesion molecule-1, play pivotal roles in inflammation. However, their role in peritoneal injury is unclear. We measured changes in intercellular adhesion molecule-1 expression in the peritoneum of a peritoneal injury model in rats. The associations between soluble intercellular adhesion molecule-1 levels in drained dialysate and the solute transport rate (D/P-Cr and D/D0-glucose) determined by the peritoneal equilibration test, and matrix metalloproteinase-2 levels in drained dialysate were investigated in 94 peritoneal drained dialysate samples. Intercellular adhesion molecule-1 expression was increased in the peritoneum of rats with peritoneal injury. Soluble intercellular adhesion molecule-1 levels in drained dialysate were significantly positively correlated with D/P-Cr (r = .51, p < .01) and inversely correlated with D/D0-glucose (r = -.44, p < .01). They were also significantly positively correlated with matrix metalloproteinase-2 levels in drained dialysate (r = .86, p < .01). Intercellular adhesion molecule-1expression is increased in the peritoneum of a peritoneal injury model in the rat, and soluble intercellular adhesion molecule-1 levels in drained dialysate are associated with peritoneal injury in patients on peritoneal dialysis. These results suggest that soluble intercellular adhesion molecule-1 could be a novel biomarker of peritoneal injury in patients on peritoneal dialysis.

  15. Intercellular adhesion molecule-1 mediates murine colon adenocarcinoma invasion.

    PubMed

    Howard, Kenton; Lo, Karen K; Ao, Lihua; Gamboni, Fabia; Edil, Barish H; Schulick, Richard; Barnett, Carlton C

    2014-03-01

    Intercellular adhesion molecule-1 (ICAM-1) modulates cell-cell adhesion and is a receptor for cognate ligands on leukocytes. Upregulation of ICAM-1 has been demonstrated in malignant transformation of adenomas and is associated with poor prognosis for many malignancies. ICAM-1 is upregulated on the invasive front of pancreatic metastases and melanomas. These data suggest that the upregulated ICAM-1 expression promotes malignant progression. We hypothesize that the downregulation of ICAM-1 will mitigate tumor progression. Mouse colon adenocarcinoma cells (MC38) were evaluated for the expression of ICAM-1 using Western immunoblot analysis. Short hairpin RNA (shRNA) transduction was used to downregulate ICAM-1. Tumor invasion determined via a modified Boyden chamber was used as a surrogate of tumor progression examining MC38 cells, MC38 ICAM-1 knockdowns, and MC38 transduced with vehicle control. The cells were cultured in full media for 24 h and serum-starved for 24 h. A total of 5 × 10(4) cells were plated and allowed to migrate for 24 h using full media with 10% fetal bovine serum as a chemoattractant. Inserts were fixed and stained with crystal violet. Blinded investigators counted the cells using a stereomicroscope. Statistical analysis was performed by analysis of variance with Fischer protected least significant difference and a P value of <0.05 was considered statistically significant. ICAM-1 was constitutively expressed on MC38 cells. Transduction with anti-ICAM-1 shRNA vector downregulated ICAM-1 protein expression by 30% according to the Western blot analysis (P < 0.03) and decreased ICAM-1 messenger RNA expression by 70% according to the reverse transcription-polymerase chain reaction. shRNA knockdown cells had a significant reduction in invasion >45% (P < 0.03). There were no significant differences between the invasion rates of MC38 and MC38 vehicle controls. Downregulation of ICAM-1 mitigates MC38 invasion. These data suggest that targeted

  16. Sulforaphane suppresses vascular adhesion molecule-1 expression in TNF-α-stimulated mouse vascular smooth muscle cells: involvement of the MAPK, NF-κB and AP-1 signaling pathways.

    PubMed

    Kim, Ji-Yun; Park, Hye-Jin; Um, Sung Hee; Sohn, Eun-Hwa; Kim, Byung-Oh; Moon, Eun-Yi; Rhee, Dong-Kwon; Pyo, Suhkneung

    2012-01-01

    Atherosclerosis is a long-term inflammatory disease of the arterial wall. Increased expression of the cell adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) is associated with increased proliferation of vascular smooth muscle cells (VSMCs), leading to increased neointima or atherosclerotic lesion formation. Therefore, the functional inhibition of adhesion molecules could be a critical therapeutic target of inflammatory disease. In the present study, we investigate the effect of sulforaphane on the expression of VCAM-1 induced by TNF-α in cultured mouse vascular smooth muscle cell lines. Pretreatment of VSMCs for 2h with sulforaphane (1-5μg/ml) dose-dependently inhibited TNF-α-induced adhesion of THP-1 monocytic cells and protein expression of VCAM-1. Sulforaphane also suppressed TNF-α-induced production of intracellular reactive oxygen species (ROS) and activation of p38, ERK and JNK. Furthermore, sulforaphane inhibited NK-κB and AP-1 activation induced by TNF-α. Sulforaphane inhibited TNF-α-induced ΙκΒ kinase activation, subsequent degradation of ΙκΒα and nuclear translocation of p65 NF-κB and decreased c-Jun and c-Fos protein level. This study suggests that sulforaphane inhibits the adhesive capacity of VSMC and downregulates the TNF-α-mediated induction of VCAM-1 in VSMC by inhibiting the MAPK, NF-κB and AP-1 signaling pathways and intracellular ROS production. Thus, sulforaphane may have beneficial effects to suppress inflammation within the atherosclerotic lesion. Copyright © 2011 Elsevier Inc. All rights reserved.

  17. Expression and polarization of intercellular adhesion molecule-1 on human intestinal epithelia: consequences for CD11b/CD18-mediated interactions with neutrophils.

    PubMed Central

    Parkos, C. A.; Colgan, S. P.; Diamond, M. S.; Nusrat, A.; Liang, T. W.; Springer, T. A.; Madara, J. L.

    1996-01-01

    BACKGROUND: Epithelial dysfunction and patient symptoms in inflammatory intestinal diseases such as ulcerative colitis and Crohn's disease correlate with migration of neutrophils (PMN) across the intestinal epithelium. In vitro modeling of PMN transepithelial migration has revealed distinct differences from transendothelial migration. By using polarized monolayers of human intestinal epithelia (T84), PMN transepithelial migration has been shown to be dependent on the leukocyte integrin CD11b/CD18 (Mac-1), but not on CD11a/CD18 (LFA-1). Since intercellular adhesion molecule-I (ICAM-1) is an important endothelial counterreceptor for these integrins, its expression in intestinal epithelia and role in PMN-intestinal epithelial interactions was investigated. MATERIALS AND METHODS: A panel of antibodies against different domains of ICAM-1, polarized monolayers of human intestinal epithelia (T84), and natural human colonic epithelia were used to examine the polarity of epithelial ICAM-1 surface expression and the functional role of ICAM-1 in neutrophil-intestinal epithelial adhesive interactions. RESULTS: While no surface expression of ICAM-1 was detected on unstimulated T84 cells, interferon-gamma (IFN gamma) elicited a marked expression of ICAM-1 that selectively polarized to the apical epithelial membrane. Similarly, apically restricted surface expression of ICAM-1 was detected in natural human colonic epithelium only in association with active inflammation. With or without IFN gamma pre-exposure, physiologically directed (basolateral-to-apical) transepithelial migration of PMN was unaffected by blocking monoclonal antibodies (mAbs) to ICAM-1. In contrast, PMN migration across IFN gamma-stimulated monolayers in the reverse (apical-to-basolateral) direction was inhibited by anti-ICAM-1 antibodies. Adhesion studies revealed that T84 cells adhered selectively to purified CD11b/CD18 and such adherence, with or without IFN gamma pre-exposure, was unaffected by ICAM-1 m

  18. Eosinophils adhere to vascular cell adhesion molecule-1 via podosomes.

    PubMed

    Johansson, Mats W; Lye, Ming H; Barthel, Steven R; Duffy, Allison K; Annis, Douglas S; Mosher, Deane F

    2004-10-01

    Vascular cell adhesion molecule (VCAM)-1 supports specific eosinophil adhesion via alpha4beta1 integrin. We tested the hypothesis that adhesive contacts formed by eosinophils on VCAM-1 are different from focal adhesions formed by adherent fibroblasts. Eosinophils adherent on VCAM-1 formed punctate adhesions that fit the criteria for podosomes, highly dynamic structures found in adherent transformed fibroblasts, osteoclasts, and macrophages. The structures contained beta1 integrin subunit, phosphotyrosine-containing proteins, punctate filamentous actin, and gelsolin, a podosome marker. In contrast, nontransformed fibroblasts on VCAM-1 formed peripheral focal adhesions that were positive for alpha4, beta1, phosphotyrosine, vinculin, talin, and paxillin; negative for gelsolin; and associated with microfilaments. Phorbol myristate acetate or tumor necrosis factor-alpha and interleukin-5 stimulated podosome formation in adherent eosinophils. Because podosomes in tumor cells are associated with extracellular matrix degradation, we analyzed the VCAM-1 layer. VCAM-1 was lost under adherent eosinophils but not under adherent fibroblasts. This loss was inhibited by the metalloproteinase inhibitor ortho-phenanthroline and correlated with expression and podosome localization of a membrane-tethered metalloproteinase, a disintegrin and metalloproteinase domain 8. Podosome-mediated VCAM-1 clearance may be a mechanism to regulate eosinophil arrest and extravasation in allergic conditions such as asthma.

  19. Triamcinolone acetonide modulates permeability and intercellular adhesion molecule-1 (ICAM-1) expression of the ECV304 cell line: implications for macular degeneration.

    PubMed

    Penfold, P L; Wen, L; Madigan, M C; Gillies, M C; King, N J; Provis, J M

    2000-09-01

    Whilst animal studies and a pilot clinical trial suggest that intravitreal triamcinolone acetonide (TA) may be useful in the treatment of age-related macular degeneration (AMD), its mode of action remains to be fully elucidated. The present study has investigated the capacity of TA to modulate the expression of adhesion molecules and permeability using a human epithelial cell line (ECV304) as a model of the outer blood-retinal barrier (BRB). The influence of TA on the expression of ICAM-1 and MHC-I was studied on resting and phorbol myristate acetate (PMA)- or interferon-gamma (IFN-gamma)- and/or tumour necrosis factor-alpha (TNF-alpha)-activated cells using flow cytometry and immunocytochemistry. Additionally, ECV304 cells were grown to confluence in uncoated Transwell chambers; transepithelial resistance (TER) across resting and PMA-activated cells was monitored. TA significantly decreased the paracellular permeability of ECV304 cells and down-regulated ICAM-1 expression, consistent with immunocytochemical observations. PMA-induced permeability changes were dose-dependent and TA decreased permeability of both resting and PMA-activated monolayers. MHC-I expression by ECV304 cells however, was not significantly affected by TA treatment. The modulation of TER and ICAM-1 expression in vitro correlate with clinical observations, suggesting re-establishment of the BRB and down-regulation of inflammatory markers are the principal effects of intravitreal TA in vivo. The results further indicate that TA has the potential to influence cellular permeability, including the barrier function of the retinal pigment epithelium (RPE) in AMD-affected retinae.

  20. Carbohydrate ligands for endothelial - Leukocyte adhesion molecule 1

    SciTech Connect

    Tiemeyer, M.; Swiedler, S.J.; Ishihara, Masayuki; Moreland, M.; Schweingruber, H.; Hirtzer, P.; Brandley, B.K. )

    1991-02-15

    The acute inflammatory response requires that circulating leukocytes bind to and penetrate the vascular wall to access the site of injury. Several receptors have been implicated in this interaction, including a family of putative carbohydrate-binding proteins. The authors report here the identification of an endogenous carbohydrate ligand for one of these receptors, endothelial-leukocyte adhesion molecule 1 (ELAM-1). Radiolabeled COS cells transfected with a plasmid containing the cDNA for ELAM-1 were used as probes to screen glycolipids extracted from human leukocytes. COS cells transfected with this plasmid adhered to a subset of sialylated glycolipids resolved on TLC plates or adsorbed on polyvinyl chloride microtiter wells. Adhesion to these glycolipids required calcium but was not inhibited by heparin, chondroitin sulfate, keratan sulfate, or yeast phosphomannan. Monosaccharide composition, linkage analysis, and fast atom bombardment mass spectrometry of the glycolipids indicate that the ligands for ELAM-1 are terminally sialylated lactosylceramides with a variable number of N-acetyllactosamine repeats and at least one fucosylated N-acetylglucosamine residue.

  1. Vascular Cell Adhesion Molecule 1, Intercellular Adhesion Molecule 1, and Cluster of Differentiation 146 Levels in Patients with Type 2 Diabetes with Complications

    PubMed Central

    Saribal, Devrim; Yenmis, Guven; Guvenen, Guvenc

    2017-01-01

    Background Type 2 diabetes mellitus (T2DM) is a multisystemic, chronic disease accompanied by microvascular complications involving various complicated mechanisms. Intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), and cluster of differentiation-146 (CD146) are mainly expressed by endothelial cells, and facilitate the adhesion and transmigration of immune cells, leading to inflammation. In the present study, we evaluated the levels of soluble adhesion molecules in patients with microvascular complications of T2DM. Methods Serum and whole blood samples were collected from 58 T2DM patients with microvascular complications and 20 age-matched healthy subjects. Levels of soluble ICAM-1 (sICAM-1) and soluble VCAM-1 (sVCAM-1) were assessed using enzyme-linked immunosorbent assay, while flow cytometry was used to determine CD146 levels. Results Serum sICAM-1 levels were lower in T2DM patients with microvascular complications than in healthy controls (P<0.05). No significant differences were found in sVCAM-1 and CD146 levels between the study and the control group. Although patients were subdivided into groups according to the type of microvascular complications that they experienced, cell adhesion molecule levels were not correlated with the complication type. Conclusion In the study group, most of the patients were on insulin therapy (76%), and 95% of them were receiving angiotensin-converting enzyme (ACE)-inhibitor agents. Insulin and ACE-inhibitors have been shown to decrease soluble adhesion molecule levels via various mechanisms, so we suggest that the decreased or unchanged levels of soluble forms of cellular adhesion molecules in our study group may have resulted from insulin and ACE-inhibitor therapy, as well as tissue-localized inflammation in patients with T2DM. PMID:28345319

  2. Intercellular Adhesion Molecule-1 (ICAM-1) in the Pathogenesis of Asthma

    NASA Astrophysics Data System (ADS)

    Wesgner, Craig D.; Gundel, Robert H.; Reilly, Patricia; Haynes, Nancy; Letts, L. Gordon; Rothlein, Robert

    1990-01-01

    Airway eosinophilia, epithelial desquamation, and hyperresponsiveness are characteristics of the airway inflammation underlying bronchial asthma. The contribution of intercellular adhesion molecule-1 (ICAM-1) to eosinophil migration and airway responsiveness was studied. ICAM-1 partially mediated eosinophil adhesion to endothelium in vitro and was upregulated on inflamed bronchial endothelium in vivo. ICAM-1 expression was also upregulated on inflamed airway epithelium in vitro and in vivo. In a primate model of asthma, a monoclonal antibody to ICAM-1 attenuated airway eosinophilia and hyperresponsiveness. Thus, antagonism of ICAM-1 may provide a therapeutic approach to reducing airway inflammation, hyperresponsiveness, and asthma symptoms.

  3. Expression of leucocyte function-associated antigen-1 and 7F7-antigen, an adhesion molecule related to intercellular adhesion molecule-1 (ICAM-1) in non-Hodgkin lymphomas and leukaemias: possible influence on growth pattern and leukaemic behaviour.

    PubMed Central

    Stauder, R; Greil, R; Schulz, T F; Thaler, J; Gattringer, C; Radaskiewicz, T; Dierich, M P; Huber, H

    1989-01-01

    In 160 non-Hodgkin lymphomas (NHL) of B and T cell origin the expression of leucocyte function-associated antigen-1 (LFA-1) and one of its counter-structures named 7F7-antigen was studied. Functional and structural similarities and the 7F7-reactivity of pICAM-1 transfected COS-cells prove that 7F7-antigen is identical with ICAM-1. The expression of both adhesion structures occurred variably and clearly depended on the maturation stage and on the B and T cell origin of lymphomas but was not associated with the proliferative status of tumour cells. The concomitant expression of both adhesion molecules was a characteristic feature of germinal centre derived NHL, particularly of those with neoplastic follicular structures (corr. contingency coeff. = 0.506; P less than 0.02), whereas both adhesion structures were less often expressed on lymphomas with a more diffuse pattern of tumour infiltration. Most B-NHL of low-grade malignancy expressed LFA-1 while their counterparts of high-grade malignancy often tended to be LFA-1 negative. In B cell neoplasias of low-grade malignancy the lack of ICAM-1 and a leukaemic course of the disease were significantly correlated (P less than 0.0005). The results indicate that the differential expression of both adhesion molecules may account for distinct patterns of growth and spread in subtypes of lymphoid malignancies. PMID:2673591

  4. Expression of leucocyte function-associated antigen-1 and 7F7-antigen, an adhesion molecule related to intercellular adhesion molecule-1 (ICAM-1) in non-Hodgkin lymphomas and leukaemias: possible influence on growth pattern and leukaemic behaviour.

    PubMed

    Stauder, R; Greil, R; Schulz, T F; Thaler, J; Gattringer, C; Radaskiewicz, T; Dierich, M P; Huber, H

    1989-08-01

    In 160 non-Hodgkin lymphomas (NHL) of B and T cell origin the expression of leucocyte function-associated antigen-1 (LFA-1) and one of its counter-structures named 7F7-antigen was studied. Functional and structural similarities and the 7F7-reactivity of pICAM-1 transfected COS-cells prove that 7F7-antigen is identical with ICAM-1. The expression of both adhesion structures occurred variably and clearly depended on the maturation stage and on the B and T cell origin of lymphomas but was not associated with the proliferative status of tumour cells. The concomitant expression of both adhesion molecules was a characteristic feature of germinal centre derived NHL, particularly of those with neoplastic follicular structures (corr. contingency coeff. = 0.506; P less than 0.02), whereas both adhesion structures were less often expressed on lymphomas with a more diffuse pattern of tumour infiltration. Most B-NHL of low-grade malignancy expressed LFA-1 while their counterparts of high-grade malignancy often tended to be LFA-1 negative. In B cell neoplasias of low-grade malignancy the lack of ICAM-1 and a leukaemic course of the disease were significantly correlated (P less than 0.0005). The results indicate that the differential expression of both adhesion molecules may account for distinct patterns of growth and spread in subtypes of lymphoid malignancies.

  5. Multinucleated giant cells generation induced by interferon-gamma. Changes in the expression and distribution of the intercellular adhesion molecule-1 during macrophages fusion and multinucleated giant cell formation.

    PubMed

    Fais, S; Burgio, V L; Silvestri, M; Capobianchi, M R; Pacchiarotti, A; Pallone, F

    1994-11-01

    Multinucleated giant cells (MGC), interferon-gamma (IFN-gamma) production, and increased expression of adhesion molecules are features of granulomatous reactions. IFN-gamma induces the fusion of macrophages and the subsequent MGC generation in vitro. Moreover, IFN-gamma increases ICAM-1 expression on lymphoid cells and an important role for adhesion molecules in MGC generation has been proposed. The time course of the IFN-gamma-driven MGC generation was investigated in slide-chamber cultures of adherence-purified human monocytes. The fusion index, the monocytes clustering the total number of MGC were determined. The expression of intercellular cell adhesion molecule-1 (ICAM-1), LFA-1 and HLA-DR was investigated by immunohistochemistry. The effect of anti-ICAM-1, anti-LFA-1 and anti-HLA-DR monoclonal antibodies on IFN-gamma-induced MGC generation was also examined. IFN-gamma enhanced the generation of MGC in a dose- and time-dependent fashion. In all experiments, MGC formation was preceded by a sequence of changes in the morphology of cultured monocytes. Cell clustering occurred as early as 3 days after IFN-gamma stimulation and was followed by the adhesion of cells that eventually fused. Immunohistochemistry showed that ICAM-1 was increased by IFN-gamma and constantly polarized on a cell uropode. When monocytes clustered, ICAM-1 was localized on the membrane where the cell-to-cell contact occurred. In newly formed MGC, ICAM-1 stained in the center of the giant cell. The cellular distribution of LFA-1 on cultured monocytes was not modified by IFN-gamma. HLA-DR expectedly enhanced by IFN-gamma was mostly cytoplasmic and tended to disappear when MGC formed. Finally, anti-LFA-1 and anti-ICAM-1 monoclonal antibodies variably inhibited IFN-gamma-induced MGC generation. Taken together, these data add support to the concept that IFN-gamma is essential for MGC generation by promoting cell clustering and cell-to-cell adhesion. The present data also indicate that among the

  6. Cloning and Stable Expression of cDNA Coding For Platelet Endothelial Cell Adhesion Molecule -1 (PECAM-1, CD31) in NIH-3T3 Cell Line.

    PubMed

    Salehi-Lalemarzi, Hamed; Shanehbandi, Dariush; Shafaghat, Farzaneh; Abbasi-Kenarsari, Hajar; Baradaran, Behzad; Movassaghpour, Ali Akbar; Kazemi, Tohid

    2015-06-01

    PECAM-1 (CD31) is a glycoprotein expressed on endothelial and bone marrow precursor cells. It plays important roles in angiogenesis, maintenance and integration of the cytoskeleton and direction of leukocytes to the site of inflammation. We aimed to clone the cDNA coding for human CD31 from KG1a for further subcloning and expression in NIH-3T3 mouse cell line. CD31 cDNA was cloned from KG1a cell line after total RNA extraction and cDNA synthesis. Pfu DNA polymerase-amplified specific band was ligated to pGEMT-easy vector and sub-cloned in pCMV6-Neo expression vector. After transfection of NIH-3T3 cells using 3 μg of recombinant construct and 6 μl of JetPEI transfection reagent, stable expression was obtained by selection of cells by G418 antibiotic and confirmed by surface flow cytometry. 2235 bp specific band was aligned completely to human CD31 reference sequence in NCBI database. Transient and stable expression of human CD31 on transfected NIH-3T3 mouse fibroblast cells was achieved (23% and 96%, respectively) as shown by flow cytometry. Due to murine origin of NIH-3T3 cell line, CD31-expressing NIH-3T3 cells could be useful as immunogen in production of diagnostic monoclonal antibodies against human CD31, with no need for purification of recombinant proteins.

  7. Angiogenesis in Platelet Endothelial Cell Adhesion Molecule-1-Null Mice

    PubMed Central

    Cao, Gaoyuan; Fehrenbach, Melane L.; Williams, James T.; Finklestein, Jeffrey M.; Zhu, Jing-Xu; DeLisser, Horace M.

    2009-01-01

    Platelet endothelial cell adhesion molecule (PECAM)-1 has been previously implicated in endothelial cell migration; additionally, anti-PECAM-1 antibodies have been shown to inhibit in vivo angiogenesis. Studies were therefore performed with PECAM-1-null mice to further define the involvement of PECAM-1 in blood vessel formation. Vascularization of subcutaneous Matrigel implants as well as tumor angiogenesis were both inhibited in PECAM-1-null mice. Reciprocal bone marrow transplants that involved both wild-type and PECAM-1-deficient mice revealed that the impaired angiogenic response resulted from a loss of endothelial, but not leukocyte, PECAM-1. In vitro wound migration and single-cell motility by PECAM-1-null endothelial cells were also compromised. In addition, filopodia formation, a feature of motile cells, was inhibited in PECAM-1-null endothelial cells as well as in human endothelial cells treated with either anti-PECAM-1 antibody or PECAM-1 siRNA. Furthermore, the expression of PECAM-1 promoted filopodia formation and increased the protein expression levels of Cdc42, a Rho GTPase that is known to promote the formation of filopodia. In the developing retinal vasculature, numerous, long filamentous filopodia, emanating from endothelial cells at the tips of angiogenic sprouts, were observed in wild-type animals, but to a lesser extent in the PECAM-1-null mice. Together, these data further establish the involvement of endothelial PECAM-1 in angiogenesis and suggest that, in vivo, PECAM-1 may stimulate endothelial cell motility by promoting the formation of filopodia. PMID:19574426

  8. P2Y2 Receptor-mediated Lymphotoxin-α Secretion Regulates Intercellular Cell Adhesion Molecule-1 Expression in Vascular Smooth Muscle Cells*

    PubMed Central

    Seye, Cheikh I.; Agca, Yuksel; Agca, Cansu; Derbigny, Wilbert

    2012-01-01

    The proinflammatory cytokine lymphotoxin-α (LTA) is thought to contribute to the pathogenesis of atherosclerosis. However, the mechanisms that regulate its expression in vascular smooth muscle cells (VSMC) are poorly understood. The ability of exogenous nucleotides to stimulate LTA production was evaluated in VSMC by ELISA. The P2Y2 nucleotide receptor (P2Y2R) agonist UTP stimulates a strong and sustained release of LTA from WT but not P2Y2R−/− SMC. Assessment of LTA gene transcription by LTA promoter-luciferase construct indicated that LTA levels are controlled at the level of transcription. We show using RNAi techniques that knockdown of the actin-binding protein filamin-A (FLNa) severely impaired nucleotide-induced Rho activation and consequent Rho-mediated LTA secretion. Reintroduction of FLNa in FLNa RNAi SMC rescued UTP-induced LTA expression. In addition, we found that UTP-stimulated LTA secretion is not sensitive to brefeldin A, which blocks the formation of vesicles involved in protein transport from the endoplasmic reticulum to the Golgi apparatus, suggesting that P2Y2R/filamin-mediated secretion of LTA is independent of the endoplasmic reticulum/Golgi secretory vesicle route. Furthermore, UTP selectively induces ICAM-1 expression in WT but not SMC expressing a truncated P2Y2R deficient in LTA secretion. These data suggest that P2Y2R recruits FLNa to provide a cytoskeletal scaffold necessary for Rho signaling pathway upstream of LTA release and subsequent stimulation of ICAM-1 expression on vascular smooth muscle cells. PMID:22298782

  9. P2Y2 receptor-mediated lymphotoxin-α secretion regulates intercellular cell adhesion molecule-1 expression in vascular smooth muscle cells.

    PubMed

    Seye, Cheikh I; Agca, Yuksel; Agca, Cansu; Derbigny, Wilbert

    2012-03-23

    The proinflammatory cytokine lymphotoxin-α (LTA) is thought to contribute to the pathogenesis of atherosclerosis. However, the mechanisms that regulate its expression in vascular smooth muscle cells (VSMC) are poorly understood. The ability of exogenous nucleotides to stimulate LTA production was evaluated in VSMC by ELISA. The P2Y(2) nucleotide receptor (P2Y(2)R) agonist UTP stimulates a strong and sustained release of LTA from WT but not P2Y(2)R(-/-) SMC. Assessment of LTA gene transcription by LTA promoter-luciferase construct indicated that LTA levels are controlled at the level of transcription. We show using RNAi techniques that knockdown of the actin-binding protein filamin-A (FLNa) severely impaired nucleotide-induced Rho activation and consequent Rho-mediated LTA secretion. Reintroduction of FLNa in FLNa RNAi SMC rescued UTP-induced LTA expression. In addition, we found that UTP-stimulated LTA secretion is not sensitive to brefeldin A, which blocks the formation of vesicles involved in protein transport from the endoplasmic reticulum to the Golgi apparatus, suggesting that P2Y(2)R/filamin-mediated secretion of LTA is independent of the endoplasmic reticulum/Golgi secretory vesicle route. Furthermore, UTP selectively induces ICAM-1 expression in WT but not SMC expressing a truncated P2Y(2)R deficient in LTA secretion. These data suggest that P2Y(2)R recruits FLNa to provide a cytoskeletal scaffold necessary for Rho signaling pathway upstream of LTA release and subsequent stimulation of ICAM-1 expression on vascular smooth muscle cells.

  10. C-reactive protein activates the nuclear factor-kappaB pathway and induces vascular cell adhesion molecule-1 expression through CD32 in human umbilical vein endothelial cells and aortic endothelial cells.

    PubMed

    Liang, Yao-Jen; Shyu, Kou-Gi; Wang, Bao-Wei; Lai, Ling-Ping

    2006-03-01

    C-reactive protein (CRP) contributes to the process of atherosclerosis by inducing pro-inflammatory changes in endothelial cells. However, the exact receptor involved in CRP-induced endothelial changes remains unclear. Human umbilical vein endothelial cells (HUVECs) and human aortic endothelial cells (HAECs) were used for the experiments. After incubation with CRP, immunoblotting showed a significant decrease of IkappaB protein and electrophoretic mobility shift assay showed a significant increase of nuclear NF-kappaB binding capacity. These changes were associated with a significant increase of vascular cell adhesion molecule-1 (VCAM-1) expression. The mRNA level of CD32, the major binding protein for CRP in endothelial cells, increased significantly as measured by Northern blot and Western blot. When these cells were transfected with siRNA directed against CD32, the mRNA of CD32 decreased significantly. The IkappaB degradation, NF-kappaB nuclear translocation and VCAM-1 up-regulation induced by CRP were all inhibited by treatment with siRNA against CD32. SB203580, a P38 inhibitor, significantly attenuated the CRP-induced responses while SP600125 (c-jun kinase inhibitor) did not. In conclusion, CRP-induced IkappaB degradation, NF-kappaB nuclear translocation and VCAM-1 protein expression in HUVECs and HAECs. CRP also increased the expression of CD32, which might serve as the receptor for CRP in endothelial cells and mediated the effects of CRP.

  11. Angiogenesis mediated by soluble forms of E-selectin and vascular cell adhesion molecule-1

    NASA Astrophysics Data System (ADS)

    Koch, Alisa E.; Halloran, Margaret M.; Haskell, Catherine J.; Shah, Manisha R.; Polverini, Peter J.

    1995-08-01

    ENDOTHELIAL adhesion molecules facilitate the entry of leukocytes into inflamed tissues. This in turn promotes neovascularization, a process central to the progression of rheumatoid arthritis, tumour growth and wound repair1. Here we test the hypothesis that soluble endothelial adhesion molecules promote angiogenesis2á¤-4. Human recombinant soluble E-selectin and soluble vascular cell adhesion molecule-1 induced chemotaxis of human endothelial cells in vitro and were angiogenic in rat cornea. Soluble E-selectin acted on endothelial cells in part through a sialyl Lewis-X-dependent mechanism, while soluble vascular cell adhesion molecule-1 acted on endothelial cells in part through a very late antigen (VLA)-4 dependent mechanism. The chemotactic activity of rheumatoid synovial fluid for endothelial cells, and also its angiogenic activity, were blocked by antibodies to either soluble E-selectin or soluble vascular cell adhesion molecule-1. These results suggest a novel function for soluble endothelial adhesion molecules as mediators of angiogenesis.

  12. The Effect of Dexmedetomidine on Oxidative Stress Response Following Cerebral Ischemia-Reperfusion in Rats and the Expression of Intracellular Adhesion Molecule-1 (ICAM-1) and S100B.

    PubMed

    Li, Yanwen; Liu, Shikun

    2017-02-17

    BACKGROUND Ischemia-reperfusion injury of whole brain involves a complicated pathophysiology mechanism. Dexmedetomidine (Dex) has been shown to have neuro protective functions. This study observed the effect of Dex on serum S100B and cerebral intracellular adhesion molecule-1 (ICAM-1) in a rat model of cerebral ischemia-reperfusion. MATERIAL AND METHODS Healthy Sprague Dawley (SD) rats (males, 7 weeks old) were randomly divided into sham, model, and Dex groups (n=20 each). A cerebral ischemia-reperfusion model was prepared by clipping of the bilateral common carotid artery combined with hypotension. Dex (9 μg/kg) was infused intravenously immediately after reperfusion in the Dex group, while the other two groups received an equal volume of saline. Neural defect score (NDS) was measured at 6 hours, 24 hours, and 72 hours after surgery, with pathological observation of brain tissues. ELISA was then used to test serum S100B protein level. Malondialdehyde (MDA) and superoxide dismutase (SOD) were assayed by spectrometry. Nuclear factor-kappa B (NF-kB) and ICAM-1 levels were determined by real-time (RT)-PCR. RESULTS Model rats had significant injury in the hippocampal CA1 region as shown by elevated NDS, S100B, and MDA levels, higher NF-κB and ICAM-1 mRNA expression, and lower SOD levels (p<0.05). Dex treatment improved pathological injury, decreased NDS, S100B, and MDA levels, decreased expression of mRNA of NF-κB and ICAM-1, and increased SOD levels. CONCLUSIONS Dex alleviated ischemia-reperfusion damage to rat brains, and inhibited NF-κB and ICAM-1 expression in brain tissues, possibly via inhibiting oxidative stress and inflammatory response.

  13. The Effect of Dexmedetomidine on Oxidative Stress Response Following Cerebral Ischemia-Reperfusion in Rats and the Expression of Intracellular Adhesion Molecule-1 (ICAM-1) and S100B

    PubMed Central

    Li, Yanwen; Liu, Shikun

    2017-01-01

    Background Ischemia-reperfusion injury of whole brain involves a complicated pathophysiology mechanism. Dexmedetomidine (Dex) has been shown to have neuro protective functions. This study observed the effect of Dex on serum S100B and cerebral intracellular adhesion molecule-1 (ICAM-1) in a rat model of cerebral ischemia-reperfusion. Material/Methods Healthy Sprague Dawley (SD) rats (males, 7 weeks old) were randomly divided into sham, model, and Dex groups (n=20 each). A cerebral ischemia-reperfusion model was prepared by clipping of the bilateral common carotid artery combined with hypotension. Dex (9 μg/kg) was infused intravenously immediately after reperfusion in the Dex group, while the other two groups received an equal volume of saline. Neural defect score (NDS) was measured at 6 hours, 24 hours, and 72 hours after surgery, with pathological observation of brain tissues. ELISA was then used to test serum S100B protein level. Malondialdehyde (MDA) and superoxide dismutase (SOD) were assayed by spectrometry. Nuclear factor-kappa B (NF-κB) and ICAM-1 levels were determined by real-time (RT)-PCR. Results Model rats had significant injury in the hippocampal CA1 region as shown by elevated NDS, S100B, and MDA levels, higher NF-κB and ICAM-1 mRNA expression, and lower SOD levels (p<0.05). Dex treatment improved pathological injury, decreased NDS, S100B, and MDA levels, decreased expression of mRNA of NF-κB and ICAM-1, and increased SOD levels. Conclusions Dex alleviated ischemia-reperfusion damage to rat brains, and inhibited NF-κB and ICAM-1 expression in brain tissues, possibly via inhibiting oxidative stress and inflammatory response. PMID:28212354

  14. Up-regulation of intercellular adhesion molecule 1 transcription by hepatitis B virus X protein.

    PubMed Central

    Hu, K Q; Yu, C H; Vierling, J M

    1992-01-01

    Intercellular adhesion molecule 1 (ICAM-1), a counter-receptor for lymphocyte function-associated antigen 1 on T cells, is critically important to a wide variety of adhesion-dependent leukocyte functions, including antigen presentation and target cell lysis. ICAM-1 expression by hepatocytes is increased in areas of inflammation and necrosis during chronic hepatitis B. Whether induction of ICAM-1 is due to the effect of inflammatory cytokines or involves a direct effect of the hepatitis B virus (HBV) remains unknown. In the present study, transfection of the HBV genome into human hepatoma cell lines resulted in enhanced expression of ICAM-1 protein and RNA in the absence of inflammation. Results of subgenomic transfections indicated that the HBV X protein (pX) induced ICAM-1 expression. Nuclear run-on assays showed that pX induced the ICAM-1 gene by increasing its rate of transcription. Although both pX and interferon gamma induced transcription of ICAM-1, addition of interferon gamma to cells expressing pX did not show an additive or synergistic effect. These results indicate that pX can directly regulate expression of ICAM-1 and may participate in the immunopathogenesis of HBV infection. Images PMID:1360668

  15. Integrin engagement mediates tyrosine dephosphorylation on platelet-endothelial cell adhesion molecule 1.

    PubMed Central

    Lu, T T; Yan, L G; Madri, J A

    1996-01-01

    Platelet-endothelial cell adhesion molecule 1 (PECAM-1, CD31) is a 130-kDa member of the immunoglobulin gene superfamily expressed on endothelial cells, platelets, neutrophils, and monocytes and plays a role during endothelial cell migration. Phosphoamino acid analysis and Western blot analysis with anti-phosphotyrosine antibody show that endothelial PECAM-1 is tyrosine-phosphorylated. Phosphorylation is decreased with endothelial cell migration on fibronectin and collagen and with cell spreading on fibronectin but not on plastic. Cell adhesion on anti-integrin antibodies is also able to specifically induce PECAM-1 dephosphorylation while concurrently inducing pp125 focal adhesion kinase phosphorylation. Inhibition of dephosphorylation with sodium orthovanadate suggests that this effect is at least partially mediated by phosphatase activity. Tyr-663 and Tyr-686 are identified as potential phosphorylation sites and mutated to phenylalanine. When expressed, both mutants show reduced PECAM-1 phosphorylation but Phe-686 mutants also show significant reversal of PECAM-1-mediated inhibition of cell migration and do not localize PECAM-1 to cell borders. Our results suggest that beta 1-integrin engagement can signal to dephosphorylate PECAM-1 and that this signaling pathway may play a role during endothelial cell migration. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 PMID:8876219

  16. Regulation of body weight and energy homeostasis by neuronal cell adhesion molecule 1.

    PubMed

    Rathjen, Thomas; Yan, Xin; Kononenko, Natalia L; Ku, Min-Chi; Song, Kun; Ferrarese, Leiron; Tarallo, Valentina; Puchkov, Dmytro; Kochlamazashvili, Gaga; Brachs, Sebastian; Varela, Luis; Szigeti-Buck, Klara; Yi, Chun-Xia; Schriever, Sonja C; Tattikota, Sudhir Gopal; Carlo, Anne Sophie; Moroni, Mirko; Siemens, Jan; Heuser, Arnd; van der Weyden, Louise; Birkenfeld, Andreas L; Niendorf, Thoralf; Poulet, James F A; Horvath, Tamas L; Tschöp, Matthias H; Heinig, Matthias; Trajkovski, Mirko; Haucke, Volker; Poy, Matthew N

    2017-08-01

    Susceptibility to obesity is linked to genes regulating neurotransmission, pancreatic beta-cell function and energy homeostasis. Genome-wide association studies have identified associations between body mass index and two loci near cell adhesion molecule 1 (CADM1) and cell adhesion molecule 2 (CADM2), which encode membrane proteins that mediate synaptic assembly. We found that these respective risk variants associate with increased CADM1 and CADM2 expression in the hypothalamus of human subjects. Expression of both genes was elevated in obese mice, and induction of Cadm1 in excitatory neurons facilitated weight gain while exacerbating energy expenditure. Loss of Cadm1 protected mice from obesity, and tract-tracing analysis revealed Cadm1-positive innervation of POMC neurons via afferent projections originating from beyond the arcuate nucleus. Reducing Cadm1 expression in the hypothalamus and hippocampus promoted a negative energy balance and weight loss. These data identify essential roles for Cadm1-mediated neuronal input in weight regulation and provide insight into the central pathways contributing to human obesity.

  17. Localization of intercellular adhesion molecule-1 (ICAM-1) in the lungs of silica-exposed mice.

    PubMed Central

    Nario, R C; Hubbard, A K

    1997-01-01

    Intercellular adhesion molecule-1 (ICAM-1) is expressed on a variety of cells including endothelial cells, alveolar epithelial cells, and alveolar macrophages. Endothelial/epithelial cell ICAM-1 participates in the migration of leukocytes out of the blood in response to pulmonary inflammation, whereas alveolar macrophage ICAM-1 may represent cell activation. Our previous studies have shown that there is increased expression of ICAM-1 in lung tissue during acute inflammation following intratracheal injection with silica particles (2 mg/mouse). This increased expression was shown to play a role, in part, in the migration of neutrophils from the circulation into the tissue parenchyma. The aim of the current work is to localize expression of ICAM-1 during acute inflammation in lungs of mice exposed to either silica or the nuisance dust, titanium dioxide. In silica-exposed mice, a significant increase in ICAM-1 was detected on day-1 and localized by immunohistochemistry to aggregates of pulmonary macrophages and to type II epithelial cells. Areas of the lung with increased ICAM-1 expression also showed increased tumor necrosis factor alpha expression. Immunocytochemical staining of bronchoalveolar lavage (BAL) cells demonstrated increased ICAM-1 expression associated with alveolar macrophages 3, 5, and 7 days following silica exposure. Finally, soluble ICAM-1 levels in the BAL fluid were significantly increased in mice exposed to silica on the same days. Titanium dioxide exposure elicited a minimal increase in expression of ICAM-1 in the lungs. These data demonstrate that exposure to the toxic particle silica specifically increases ICAM-1 expression localized to pulmonary macrophages and type II epithelial cells. Images Figure 2. B Figure 2. A Figure 2. D Figure 2. C Figure 3. A Figure 3. B Figure 5. B Figure 5. A Figure 5. C PMID:9400721

  18. Role of Intercellular Adhesion Molecule-1 in Radiation-Induced Brain Injury

    SciTech Connect

    Wu, K.-L.; Tu Ba; Li Yuqing; Wong, C. Shun

    2010-01-15

    Purpose: To determine the role of intercellular adhesion molecule-1 (ICAM-1) in the pathogenesis of brain injury after irradiation (IR). Methods and Materials: We assessed the expression of ICAM-1 in mouse brain after cranial IR and determined the histopathologic and behavioral changes in mice that were either wildtype (+/+) or knockout (-/-) of the ICAM-1 gene after IR. Results: There was an early dose-dependent increase in ICAM-1 mRNA and protein expression after IR. Increased ICAM-1 immunoreactivity was observed in endothelia and glia of ICAM-1+/+ mice up to 8 months after IR. ICAM-1-/- mice showed no expression. ICAM-1+/+ and ICAM-1-/- mice showed similar vascular abnormalities at 2 months after 10-17 Gy, and there was evidence for demyelination and inhibition of hippocampal neurogenesis at 8 months after 10 Gy. After 10 Gy, irradiated ICAM-1+/+ and ICAM-1-/- mice showed similar behavioral changes at 2-6 months in open field, light-dark chamber, and T-maze compared with age-matched genotype controls. Conclusion: There is early and late upregulation of ICAM-1 in the vasculature and glia of mouse brain after IR. ICAM-1, however, does not have a causative role in the histopathologic injury and behavioral dysfunction after moderate single doses of cranial IR.

  19. Lack of Platelet Endothelial Cell Adhesion Molecule-1 Attenuates Foreign Body Inflammation because of Decreased Angiogenesis

    PubMed Central

    Solowiej, Anna; Biswas, Purba; Graesser, Donnasue; Madri, Joseph A.

    2003-01-01

    Platelet endothelial cell adhesion molecule-1 (PECAM-1, CD31) is a 130-kd member of the immunoglobulin superfamily of proteins, expressed on endothelial cells, leukocytes, and platelets. Antibody-blocking studies have implicated it in modulating leukocyte transmigration and angiogenesis. However, the generation of the PECAM-1 knockout mouse has shown that its function can be compensated for by similarly acting proteins because most acute inflammatory models proceed in a comparable manner in wild-type and knockout animals. We decided to examine the function of PECAM-1 in the chronic process of foreign body inflammation. We show that PECAM-1-deficient mice exhibit attenuated neutrophil infiltration in and around a subcutaneous polyvinyl acetyl implant. Bone marrow engraftment studies indicate that the lack of CD31 expression on the endothelium determines the diminished leukocyte accumulation in the knockout implants. Specifically, we find that decreased angiogenesis (as manifested by lower vessel density, decreased hemoglobin content, and less laminin deposition) correlates with lower neutrophil accumulation in the knockout animals. This study indicates that the absence of endothelial PECAM-1 results in decreased angiogenesis and therefore in diminished delivery of leukocytes to the foreign body implants. PMID:12598328

  20. Monocyte adhesion to endothelium in simian immunodeficiency virus-induced AIDS encephalitis is mediated by vascular cell adhesion molecule-1/alpha 4 beta 1 integrin interactions.

    PubMed Central

    Sasseville, V. G.; Newman, W.; Brodie, S. J.; Hesterberg, P.; Pauley, D.; Ringler, D. J.

    1994-01-01

    Because the mechanisms associated with recruitment of monocytes to brain in AIDS encephalitis are unknown, we used tissues from rhesus monkeys infected with simian immunodeficiency virus (SIV) to examine the relative contributions of various adhesion pathways in mediating monocyte adhesion to endothelium from encephalitic brain. Using a modified Stamper and Woodruff tissue adhesion assay, we found that the human monocytic cell lines, THP-1 and U937, and the B cell line, Ramos, preferentially bound to brain vessels from monkeys with AIDS encephalitis. Using a combined tissue adhesion/immunohistochemistry approach, these cells only bound to vessels expressing vascular cell adhesion molecule-1 (VCAM-1). Furthermore, pretreatment of tissues with antibodies to VCAM-1 or cell lines with antibodies to VLA-4 (CD49d) inhibited adhesion by more than 70%. Intercellular adhesion molecule-1 (ICAM-1)/beta 2 integrin interactions were not significant in mediating cell adhesion to the vasculature in encephalitic simian brain using a cell line (JY) capable of binding rhesus monkey ICAM-1. In addition, selectin-mediated interactions did not significantly contribute to cell binding to encephalitic brain as there was no immunohistochemical expression of E-selectin and P-selectin in either normal or encephalitic brain, nor was there a demonstrable adhesive effect from L-selectin using L-selectin-transfected 300.19 cells on simian encephalitic brain. These results demonstrate that using the tissue adhesion assay, THP-1, U937, and Ramos cells bind to vessels in brain from animals with AIDS encephalitis using VCAM-1/alpha 4 beta 1 integrin interactions and suggest that VCAM-1 and VLA-4 may be integral for monocyte recruitment to the central nervous system during the development of AIDS encephalitis. Images Figure 1 PMID:7507300

  1. Role of intercellular adhesion molecule-1 in glucan-induced pulmonary granulomatosis in the rat.

    PubMed

    Barton, P A; Imlay, M M; Flory, C M; Warren, J S

    1996-08-01

    Glucan-induced pulmonary granulomatous vasculitis in the rat mimics several human lung diseases (e.g., Wegener's granulomatosis, intravenous talcosis). We sought to clarify the role of intercellular adhesion molecule-1 (ICAM-1) in the pathogenesis of glucan-induced granulomatous vasculitis. Immunohistochemical analysis of lung sections from rats with florid vasculitis (48 hours) revealed marked alveolar septal and lesional expression of ICAM-1. An ex vivo binding analysis with isotope-labeled antibodies and lung sections taken at various times up to 48 hours after glucan infusion revealed a progressive increase in whole-lung ICAM-1 expression. In vivo measurements of vascular wall-associated ICAM-1 expression revealed an earlier rise that began less than 6 hours after glucan infusion, peaked at 24 to 48 hours, and then declined to near baseline during the ensuing 24 to 96 hours. To assess whether ICAM-1 expression both within blood vessel walls and within lesions per se is important in granuloma development, we carried out in vivo neutralization experiments with several different routes of administration of antibody to ICAM-1. Monoclonal antibody to rat ICAM-1 was either infused intravenously at time 0 (when glucan was infused), infused intravenously at time 0 and after 24 hours, instilled only intratracheally 24 hours after glucan infusion, or given both intravenously (time = 0 and 24 hours) and intratracheally (time = 24 hours). Infusions of monoclonal antibody to rat ICAM-1 resulted in dose-dependent reductions in mean granuloma number and cross-sectional area. Intrapulmonary instillation of antibody to rat ICAM-1 (via tracheostomy 24 hours after glucan infusion) resulted in a modest reduction in mean granuloma number and cross-sectional area. When antibody to ICAM-1 was both infused and instilled via the trachea, we found an additive reduction in mean granuloma size and number. There was a 12-fold increase in adhesion of ED-1-positive peripheral blood

  2. Targeting sites of inflammation: intercellular adhesion molecule-1 as a target for novel inflammatory therapies

    PubMed Central

    Hua, Susan

    2013-01-01

    Targeted drug delivery to sites of inflammation will provide effective, precise, and safe therapeutic interventions for treatment of diverse disease conditions, by limiting toxic side effects and/or increasing drug action. Disease-site targeting is believed to play a major role in the enhanced efficacy observed for a variety of drugs when formulated inside lipid vesicles. This article will focus on the factors and mechanisms involved in drug targeting to sites of inflammation and the importance of cell adhesion molecules, in particular intercellular adhesion molecule-1, in this process. PMID:24109453

  3. Differential up-regulation of circulating soluble and endothelial cell intercellular adhesion molecule-1 in mice.

    PubMed Central

    Komatsu, S.; Flores, S.; Gerritsen, M. E.; Anderson, D. C.; Granger, D. N.

    1997-01-01

    Although circulating levels of soluble intercellular adhesion molecule-1 (sICAM-1) are frequently used as an indicator of the severity of different immune, inflammatory, or neoplastic diseases, little is known about the factors that govern plasma sICAM-1 concentration and its relationship to the membranous form of ICAM-1 (mICAM-1) expressed on vascular endothelial cells. Plasma sICAM-1 concentration (measured by enzyme-linked immunosorbent assay) and mICAM-1 expression (measured using the dual radiolabeled monoclonal antibody technique) in different vascular beds (eg, lung, small intestine, and spleen) were monitored in wild-type (C57BL) and ICAM-1-deficient mice, before and after administration of tumor necrosis factor (TNF)-alpha. In wild-type mice, TNF-alpha elicited time-dependent increases in lung and intestine mICAM-1 (plateau achieved at 12 hours), with a corresponding increase in plasma sICAM-1 (peaked at 5 hours and then declined). The initial increases in mICAM-1 and pulmonary leukocyte sequestration (measured as lung myeloperoxidase activity) induced by TNF-alpha preceded any detectable elevation in sICAM-1. In ICAM-1-deficient mice, plasma sICAM-1 was reduced by approximately 70%, with > 95% reductions of mICAM-1 in lung and intestine, and > 75% reduction in splenic accumulation of anti-ICAM-1 antibody. Although TNF-alpha doubled plasma sICAM-1 in ICAM-1-deficient mice, mICAM-1 was unaffected in all tissues. Either splenectomy or pretreatment with cycloheximide resulted in an attenuated TNF-induced increase in sICAM-1, without affecting mICAM-1 expression. These findings indicate that plasma sICAM-1 concentration does not accurately reflect the level of ICAM-1 expression on endothelial cells in different vascular beds. PMID:9212746

  4. Down syndrome cell adhesion molecule 1: testing for a role in insect immunity, behaviour and reproduction

    PubMed Central

    Wensing, Kristina U.; Eggert, Hendrik; Scharsack, Jörn P.

    2016-01-01

    Down syndrome cell adhesion molecule 1 (Dscam1) has wide-reaching and vital neuronal functions although the role it plays in insect and crustacean immunity is less well understood. In this study, we combine different approaches to understand the roles that Dscam1 plays in fitness-related contexts in two model insect species. Contrary to our expectations, we found no short-term modulation of Dscam1 gene expression after haemocoelic or oral bacterial exposure in Tribolium castaneum, or after haemocoelic bacterial exposure in Drosophila melanogaster. Furthermore, RNAi-mediated Dscam1 knockdown and subsequent bacterial exposure did not reduce T. castaneum survival. However, Dscam1 knockdown in larvae resulted in adult locomotion defects, as well as dramatically reduced fecundity in males and females. We suggest that Dscam1 does not always play a straightforward role in immunity, but strongly influences behaviour and fecundity. This study takes a step towards understanding more about the role of this intriguing gene from different phenotypic perspectives. PMID:27152227

  5. Down syndrome cell adhesion molecule 1: testing for a role in insect immunity, behaviour and reproduction.

    PubMed

    Peuß, Robert; Wensing, Kristina U; Woestmann, Luisa; Eggert, Hendrik; Milutinović, Barbara; Sroka, Marlene G U; Scharsack, Jörn P; Kurtz, Joachim; Armitage, Sophie A O

    2016-04-01

    Down syndrome cell adhesion molecule 1 (Dscam1) has wide-reaching and vital neuronal functions although the role it plays in insect and crustacean immunity is less well understood. In this study, we combine different approaches to understand the roles that Dscam1 plays in fitness-related contexts in two model insect species. Contrary to our expectations, we found no short-term modulation of Dscam1 gene expression after haemocoelic or oral bacterial exposure in Tribolium castaneum, or after haemocoelic bacterial exposure in Drosophila melanogaster. Furthermore, RNAi-mediated Dscam1 knockdown and subsequent bacterial exposure did not reduce T. castaneum survival. However, Dscam1 knockdown in larvae resulted in adult locomotion defects, as well as dramatically reduced fecundity in males and females. We suggest that Dscam1 does not always play a straightforward role in immunity, but strongly influences behaviour and fecundity. This study takes a step towards understanding more about the role of this intriguing gene from different phenotypic perspectives.

  6. Human Dermal Mast Cells Contain and Release Tumor Necrosis Factor α, which Induces Endothelial Leukocyte Adhesion Molecule 1

    NASA Astrophysics Data System (ADS)

    Walsh, Laurence J.; Trinchieri, Giorgio; Waldorf, Heidi A.; Whitaker, Diana; Murphy, George F.

    1991-05-01

    Tumor necrosis factor α (TNF-α) is a proinflammatory cytokine that mediates endothelial leukocyte interactions by inducing expression of adhesion molecules. In this report, we demonstrate that human dermal mast cells contain sizeable stores of immunoreactive and biologically active TNF-α within granules, which can be released rapidly into the extracellular space upon degranulation. Among normal human dermal cells, mast cells are the predominant cell type that expresses both TNF-α protein and TNF-α mRNA. Moreover, induction of endothelial leukocyte adhesion molecule 1 expression is a direct consequence of release of mast cell-derived TNF-α. These findings establish a role for human mast cells as "gatekeepers" of the dermal microvasculature and indicate that mast cell products other than vasoactive amines influence endothelium in a proinflammatory fashion.

  7. Active Site Formation, Not Bond Kinetics, Limits Adhesion Rate between Human Neutrophils and Immobilized Vascular Cell Adhesion Molecule 1

    PubMed Central

    Waugh, Richard E.; Lomakina, Elena B.

    2009-01-01

    Abstract The formation of receptor ligand bonds at the interface between different cells and between cells and substrates is a widespread phenomenon in biological systems. Physical measurements of bond formation rates between cells and substrates have been exploited to increase our understanding of the biophysical mechanisms that regulate bond formation at interfaces. Heretofore, these measurements have been interpreted in terms of simple bimolecular reaction kinetics. Discrepancies between this simple framework and the behavior of neutrophils adhering to surfaces expressing vascular cell adhesion molecule 1 (VCAM-1) motivated the development of a new kinetic framework in which the explicit formation of active bond formation sites (reaction zones) are a prerequisite for bond formation to occur. Measurements of cells interacting with surfaces having a wide range of VCAM-1 concentrations, and for different durations of contact, enabled the determination of novel kinetic rate constants for the formation of reaction zones and for the intrinsic bond kinetics. Comparison of these rates with rates determined previously for other receptor-ligand pairs points to a predominant role of extrinsic factors such as surface topography and accessibility of active molecules to regions of close contact in determining forward rates of bond formation at cell interfaces. PMID:19134479

  8. Naringin has an antiatherogenic effect with the inhibition of intercellular adhesion molecule-1 in hypercholesterolemic rabbits.

    PubMed

    Choe, S C; Kim, H S; Jeong, T S; Bok, S H; Park, Y B

    2001-12-01

    Naringin, a bioflavonoid found in citrus fruit peel, is known to have an antioxidative effect, but its effect on atherosclerosis has not been studied. This study evaluated the effect of naringin on blood lipid levels and aortic fatty streaks, and its action mechanism in hypercholesterolemic rabbits. Male New Zealand white rabbits were fed a 0.25% cholesterol diet and divided into an untreated group (n = 4), a naringin-treated group (n = 5; 500 mg/kg per day), and a lovastatin-treated group (n = 5; 20 mg/kg per day). After 8 weeks, blood was sampled and analyzed biochemically. Aorta and liver were harvested and examined histologically. Cholesterol level in rabbits fed the 0.25% cholesterol diet reached 17 times normal and decreased in the rabbits fed naringin and lovastatin, whose effects were not statistically significant (p > 0.05). However, both naringin and lovastatin effectively decreased the area of fatty streak in thoracic aorta on macroscopic analysis (p < 0.05) and significantly reduced subintimal foam cell infiltration on microscopic morphometry (p < 0.05). These foam cells were macrophages on immunohistochemical analysis. Naringin treatment inhibited hypercholesterolemia-induced intercellular adhesion molecule-1 (ICAM-1) expression on endothelial cells. Hypercholesterolemia caused fatty liver and elevation of liver enzymes, which was prevented by naringin but not by lovastatin. Naringin significantly reduced fatty streak formation and neointimal macrophage infiltration and also inhibited the expression of ICAM-1 in endothelial cells, suggesting that suppression of ICAM-1 contributed to the antiatherogenic effect. Naringin, unlike lovastatin, has a hepatoprotective action.

  9. MITF is a critical regulator of the carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) in malignant melanoma.

    PubMed

    Ullrich, Nico; Löffek, Stefanie; Horn, Susanne; Ennen, Marie; Sánchez-Del-Campo, Luis; Zhao, Fang; Breitenbuecher, Frank; Davidson, Irwin; Singer, Bernhard B; Schadendorf, Dirk; Goding, Colin R; Helfrich, Iris

    2015-11-01

    The multifunctional Ig-like carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is neo-expressed in the majority of malignant melanoma lesions. CEACAM1 acts as a driver of tumor cell invasion, and its expression correlates with poor patient prognosis. Despite its importance in melanoma progression, how CEACAM1 expression is regulated is largely unknown. Here, we show that CEACAM1 expression in melanoma cell lines and melanoma tissue strongly correlates with that of the microphthalmia-associated transcription factor (MITF), a key regulator of melanoma proliferation and invasiveness. MITF is revealed as a direct and positive regulator for CEACAM1 expression via binding to an M-box motif located in the CEACAM1 promoter. Taken together, our study provides novel insights into the regulation of CEACAM1 expression and suggests an MITF-CEACAM1 axis as a potential determinant of melanoma progression.

  10. R-Ras Regulates Murine T Cell Migration and Intercellular Adhesion Molecule-1 Binding

    PubMed Central

    Yan, Xiaocai; Yan, Mingfei; Guo, Yihe; Singh, Gobind; Chen, Yuhong; Yu, Mei; Wang, Demin; Hillery, Cheryl A.; Chan, Andrew M.

    2015-01-01

    The trafficking of T-lymphocytes to peripheral draining lymph nodes is crucial for mounting an adaptive immune response. The role of chemokines in the activation of integrins via Ras-related small GTPases has been well established. R-Ras is a member of the Ras-subfamily of small guanosine-5’-triphosphate-binding proteins and its role in T cell trafficking has been investigated in R-Ras null mice (Rras−/−). An examination of the lymphoid organs of Rras−/− mice revealed a 40% reduction in the cellularity of the peripheral lymph nodes. Morphologically, the high endothelial venules of Rras−/− mice were more disorganized and less mature than those of wild-type mice. Furthermore, CD4+ and CD8+ T cells from Rras−/− mice had approximately 42% lower surface expression of L-selectin/CD62L. These aberrant peripheral lymph node phenotypes were associated with proliferative and trafficking defects in Rras−/− T cells. Furthermore, R-Ras could be activated by the chemokine, CCL21. Indeed, Rras−/− T cells had approximately 14.5% attenuation in binding to intercellular adhesion molecule 1 upon CCL21 stimulation. Finally, in a graft-versus host disease model, recipient mice that were transfused with Rras−/− T cells showed a significant reduction in disease severity when compared with mice transplanted with wild-type T cells. These findings implicate a role for R-Ras in T cell trafficking in the high endothelial venules during an effective immune response. PMID:26710069

  11. Oldenlandia diffusa suppresses metastatic potential through inhibiting matrix metalloproteinase-9 and intercellular adhesion molecule-1 expression via p38 and ERK1/2 MAPK pathways and induces apoptosis in human breast cancer MCF-7 cells.

    PubMed

    Chung, Tae-Wook; Choi, Hyunju; Lee, Ji-Min; Ha, Sun-Hyung; Kwak, Choong-Hwan; Abekura, Fukushi; Park, Jun-Young; Chang, Young-Chae; Ha, Ki-Tae; Cho, Seung-Hak; Chang, Hyeun Wook; Lee, Young-Choon; Kim, Cheorl-Ho

    2017-01-04

    Oldenlandia diffusa (OD) has long been known as an apoptotic inducer in breast tumors in ethnomedicine. To scientifically confirm the anti-breast cancer effects of water, methanol (MeOH) and butanol (BuOH) extracts of O. diffusa on cell apoptosis, matrix metalloproteinases (MMPs), intercellular adhesion molecule (ICAM)-1 and intracellular signaling in MCF-7 breast cancer cells. MeOH extracts (MOD) and BuOH extracts (BOD) were prepared and examined for their ability to inhibit phorbol myristate acetate (PMA)-induced matrix metalloproteinase (MMP)-9 and intercellular adhesion molecule (ICAM)-1 expressions in MCF-7 human breast cancer cells. Additionally, transwell migration, invasion and transcriptional activity were assessed. Results of immunofluorescence confocal microscopy for translocation of NF-κB and p-ERK and p-p38 were also checked. Finally, apoptotic signals including processed caspase-8, caspase-7, poly ADP-ribose polymerase, Bax and Bcl-2 were examined. MOD and BOD specifically inhibited PMA-induced MMP-9 expression as well as invasive and migration potential via ICAM-1. The inhibitory activity was also based on the suppressed transcriptional activity in MCF-7 breast cancer cells. Results of immunofluorescence confocal microscopy showed that translocation of NF-κB decreased upon BOD and MOD treatments, with a decreased level of p-ERK and p-p38 phosphorylation. In addition, treatment of MCF-7 cells with MOD and BOD activated apoptosis-linked proteins including enzymatically active forms of processed caspase-8, caspase-7 and poly ADP-ribose polymerase, together with increased expression of mitochondrial apoptotic protein, Bax and decreased expression of Bcl-2. The results indicate that OD as an anti-metastatic agent suppresses the metastatic response by targeting p-ERK, p-38 and NF-κB, thus reducing the invasion capacity of MCF-7 breast cancer cells through inhibition of MMP-9 and ICAM-1 expression and plays an important role in the regulation of breast

  12. Involvement of oxidative stress and mucosal addressin cell adhesion molecule-1 (MAdCAM-1) in inflammatory bowel disease

    PubMed Central

    Tanida, Satoshi; Mizoshita, Tsutomu; Mizushima, Takashi; Sasaki, Makoto; Shimura, Takaya; Kamiya, Takeshi; Kataoka, Hiromi; Joh, Takashi

    2011-01-01

    The pathophysiology of inflammatory bowel disease involves excessive immune effects of inflammatory cells against gut microbes. In genetically predisposed individuals, these effects are considered to contribute to the initiation and perpetuation of mucosal injury. Oxidative stress is a fundamental tissue-destructive mechanisms that can occur due to the reactive oxygen species and reactive nitrogen metabolites which are released in abundance from numerous inflammatory cells that have extravasated from lymphatics and blood vessels to the lamina propria. This extravasation is mediated by interactions between adhesion molecules including mucosal addressin cell adhesion molecule-1 and vascular cell adhesion molecule-1 on the surface of lymphocytes or neutrophils and their ligands on endothelial cells. Thus, reactive oxygen species and adhesion molecules play an important role in the development of inflammatory bowel disease. The present review focuses on the involvement of oxidative stress and adhesion molecules, in particular mucosal addressin cell adhesion molecule-1, in inflammatory bowel disease. PMID:21373262

  13. Reduction of atherosclerosis in cholesterol-fed rabbits and decrease of expressions of intracellular adhesion molecule-1 and vascular endothelial growth factor in foam cells by a water-soluble fraction of Polygonum multiflorum.

    PubMed

    Yang, Peng-Yuan; Almofti, Mohamad Radwan; Lu, Ling; Kang, Hui; Zhang, Jing; Li, Tie-Jun; Rui, Yao-Cheng; Sun, Lian-Na; Chen, Wan-Sheng

    2005-11-01

    Polygonum multiflorum stilbeneglycoside (PMS) is a water-soluble fraction of Polygonum multiflorum Thunb., one of the most famous tonic traditional Chinese medicines, that has protective effects on the cardiovascular system. The purpose of the present study is to elucidate the effects of PMS on macrophage-derived foam cell functions and the reduction of severity of atherosclerosis in hypercholesterolemic New Zealand White (NZW) rabbits. NZW rabbits were fed for 12 weeks with a normal diet, a high cholesterol diet, or a high cholesterol diet associated with irrigation with different doses of PMS (25, 50, or 100 mg/kg). Treatment of NZW rabbits fed with high cholesterol diet with 100 mg/kg PMS attenuated the increase in plasma cholesterol, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, and plasma triglyceride. Treatment with 50 and 100 mg/kg PMS caused 43% and 60% decrease in atherosclerotic lesioned area ratio to total surface area, respectively. In U937 foam cells, PMS could decrease the high expression of intercellular adhesion molecule (ICAM)-1 protein and the vascular endothelial growth factor (VEGF) protein levels in the medium induced by oxidized lipoprotein when analyzed by flow cytometry. The results proved that PMS is a powerful agent against atherosclerosis and that PMS action could possibly be through the inhibition of the expression of ICAM-1 and VEGF in foam cells.

  14. Intercellular adhesion molecule-1 blockade attenuates inflammatory response and improves microvascular perfusion in rat pancreas grafts.

    PubMed

    Preissler, Gerhard; Eichhorn, Martin; Waldner, Helmut; Winter, Hauke; Kleespies, Axel; Massberg, Steffen

    2012-10-01

    After pancreas transplantation (PTx), early capillary malperfusion and leukocyte recruitment indicate the manifestation of severe ischemia/reperfusion injury (IRI). Oscillatory blood-flow redistribution (intermittent capillary perfusion, IP), leading to an overall decrease in erythrocyte flux, precedes complete microvascular perfusion failure with persistent blood flow cessation. We addressed the role of intercellular adhesion molecule-1 (ICAM-1) for leukocyte-endothelial interactions (LEIs) after PTx and evaluated the contribution of IP and malperfusion. Pancreas transplantation was performed in rats after 18-hour preservation, receiving either isotype-matched IgG or monoclonal anti-ICAM-1 antibodies (10 mg/kg intravenously) once before reperfusion. Leukocyte-endothelial interaction, IP, erythrocyte flux, and functional capillary density, respectively, were examined in vivo during 2-hour reperfusion. Nontransplanted animals served as controls. Tissue samples were analyzed by histomorphometry. In grafts of IgG-treated animals, IP was encountered already at an early stage after reperfusion and steadily increased over 2 hours, whereas erythrocyte flux declined continuously. In contrast, inhibition of ICAM-1 significantly improved erythrocyte flux and delayed IP appearance by 2 hours. Further, anti-ICAM-1 significantly reduced LEI and leukocyte tissue infiltration when compared to IgG; edema development was less pronounced in response to anti-ICAM-1 monoclonal antibody. Intercellular adhesion molecule-1 blockade significantly attenuates IRI via immediate reduction of LEI and concomitant improvement of capillary perfusion patterns, emphasizing its central role during IRI in PTx.

  15. 5,7-Dihydroxy-3,4,6-trimethoxyflavone inhibits intercellular adhesion molecule 1 and vascular cell adhesion molecule 1 via the Akt and nuclear factor-κB-dependent pathway, leading to suppression of adhesion of monocytes and eosinophils to bronchial epithelial cells

    PubMed Central

    Jung, Jireh; Ko, Su H; Yoo, Do Y; Lee, Jin Y; Kim, Yeong-Jeon; Choi, Seul M; Kang, Kyung K; Yoon, Ho J; Kim, Hyeyoung; Youn, Jeehee; Kim, Jung M

    2012-01-01

    5,7-Dihydroxy-3′,4′,6′-trimethoxyflavone (eupatilin), the active pharmacological ingredient from Artemisia asiatica Nakai (Asteraceae), is reported to have a variety of anti-inflammatory properties in intestinal epithelial cells. However, little information is known about the molecular mechanism of eupatilin-induced attenuation of bronchial epithelial inflammation. This study investigates the role of eupatilin in the adhesion of inflammatory cells such as monocytes and eosinophils to bronchial epithelial cells. Stimulation of a human bronchial epithelial cell line (BEAS-2B) with tumour necrosis factor-α (TNF-α) increased the expression of surface adhesion molecules, including intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1), in which eupatilin significantly inhibited the expression of those adhesion molecules in a dose-dependent manner. Eupatilin suppressed the TNF-α-induced activation of IκBα and nuclear factor-κB (NF-κB) signals in BEAS-2B cells. The IκB kinase (IKK) activation was also significantly reduced in eupatilin-pre-treated BEAS-2B and primary normal human bronchial epithelial (NHBE) cells. However, eupatilin did not influence AP-1 activity in TNF-α-stimulated cells. Suppression of NF-κB signalling induced by eupatilin resulted in the inhibition of the expression of adhesion molecules and the adhesion of monocytes and eosinophils to BEAS-2B cells. Furthermore, eupatilin suppressed the phosphorylation of Akt in TNF-α-stimulated BEAS-2B and NHBE cells, leading to down-regulation of NF-κB activation and adhesion molecule expression and finally to suppression of the inflammatory cell adhesion to epithelial cells. These results suggest that eupatilin can inhibit the adhesion of inflammatory cells to bronchial epithelial cells via a signalling pathway, including activation of Akt and NF-κB, as well as expression of adhesion molecules. PMID:22862554

  16. 5,7-Dihydroxy-3,4,6-trimethoxyflavone inhibits intercellular adhesion molecule 1 and vascular cell adhesion molecule 1 via the Akt and nuclear factor-κB-dependent pathway, leading to suppression of adhesion of monocytes and eosinophils to bronchial epithelial cells.

    PubMed

    Jung, Jireh; Ko, Su H; Yoo, Do Y; Lee, Jin Y; Kim, Yeong-Jeon; Choi, Seul M; Kang, Kyung K; Yoon, Ho J; Kim, Hyeyoung; Youn, Jeehee; Kim, Jung M

    2012-09-01

    5,7-Dihydroxy-3',4',6'-trimethoxyflavone (eupatilin), the active pharmacological ingredient from Artemisia asiatica Nakai (Asteraceae), is reported to have a variety of anti-inflammatory properties in intestinal epithelial cells. However, little information is known about the molecular mechanism of eupatilin-induced attenuation of bronchial epithelial inflammation. This study investigates the role of eupatilin in the adhesion of inflammatory cells such as monocytes and eosinophils to bronchial epithelial cells. Stimulation of a human bronchial epithelial cell line (BEAS-2B) with tumour necrosis factor-α (TNF-α) increased the expression of surface adhesion molecules, including intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1), in which eupatilin significantly inhibited the expression of those adhesion molecules in a dose-dependent manner. Eupatilin suppressed the TNF-α-induced activation of IκBα and nuclear factor-κB (NF-κB) signals in BEAS-2B cells. The IκB kinase (IKK) activation was also significantly reduced in eupatilin-pre-treated BEAS-2B and primary normal human bronchial epithelial (NHBE) cells. However, eupatilin did not influence AP-1 activity in TNF-α-stimulated cells. Suppression of NF-κB signalling induced by eupatilin resulted in the inhibition of the expression of adhesion molecules and the adhesion of monocytes and eosinophils to BEAS-2B cells. Furthermore, eupatilin suppressed the phosphorylation of Akt in TNF-α-stimulated BEAS-2B and NHBE cells, leading to down-regulation of NF-κB activation and adhesion molecule expression and finally to suppression of the inflammatory cell adhesion to epithelial cells. These results suggest that eupatilin can inhibit the adhesion of inflammatory cells to bronchial epithelial cells via a signalling pathway, including activation of Akt and NF-κB, as well as expression of adhesion molecules.

  17. Toxoplasma gondii tachyzoites cross retinal endothelium assisted by intercellular adhesion molecule-1 in vitro.

    PubMed

    Furtado, João M; Bharadwaj, Arpita S; Chipps, Timothy J; Pan, Yuzhen; Ashander, Liam M; Smith, Justine R

    2012-10-01

    Retinal infection is the most common clinical manifestation of toxoplasmosis. The route by which circulating Toxoplasma gondii tachyzoites cross the vascular endothelium to enter the human retina is unknown. Convincing studies using murine encephalitis models have strongly implicated leukocyte taxis as one pathway used by the parasite to access target organs. To establish whether tachyzoites might also interact directly with vascular endothelium, we populated a transwell system with human ocular endothelial cells. Human retinal endothelial monolayers permitted transmigration of tachyzoites of RH and three natural isolate strains. Antibody blockade of intercellular adhesion molecule-1 significantly reduced this migration, but did not impact tachyzoite movement across an endothelial monolayer derived from the choroid, which lies adjacent to the retina within the eye. In demonstrating that tachyzoites are capable of independent migration across human vascular endothelium in vitro, this study carries implications for the development of therapeutics aimed at preventing access of T. gondii to the retina.

  18. Benzo[a]pyrene induces intercellular adhesion molecule-1 through a caveolae and aryl hydrocarbon receptor mediated pathway

    SciTech Connect

    Oesterling, Elizabeth; Toborek, Michal; Hennig, Bernhard

    2008-10-15

    Toxicologic and epidemiologic studies have linked benzo[a]pyrene (B[a]P) exposure with cardiovascular diseases such as atherosclerosis. The mechanisms of action leading to these diseases have not been fully understood. One key step in the development of atherosclerosis is vascular endothelial dysfunction, which is characterized by increased adhesiveness. To determine if B[a]P could lead to increased endothelial adhesiveness, the effects of B[a]P on human endothelial cell intercellular adhesion molecule-1 (ICAM-1) expression was investigated. B[a]P was able to increase ICAM-1 protein only after pretreatment with the aryl hydrocarbon receptor (AhR) agonist {beta}-naphthoflavone ({beta}-NF). Knockdown of AhR by siRNA or treatment with AhR antagonist {alpha}-naphthoflavone ({alpha}-NF) eliminated the induction of ICAM-1 from B[a]P, confirming the necessity of AhR in this process. Likewise, B[a]P only increased monocyte adhesion to the vascular endothelium when cells were pretreated with {beta}-NF. Experiments were done to define a signaling mechanism. B[a]P increased phosphorylation of MEK and p38-MAPK, and inhibitors to these proteins blunted the ICAM-1 induction. B[a]P was also able to increase AP-1 DNA binding and phosphorylation of cJun. Phosphorylation of cJun was disrupted by MEK and p38-MAPK inhibitors linking the signaling cascade. Finally, the importance of membrane microdomains, caveolae, was demonstrated by knockdown of the structural protein caveolin-1. Disruption of caveolae eliminated the B[a]P-induced ICAM-1 expression. These data suggest a possible pro-inflammatory mechanism of action of B[a]P involving caveolae, leading to increased vascular endothelial adhesiveness, and this inflammation may be a critical step in the development of B[a]P-induced atherosclerosis.

  19. Structural organization and function of mouse photoreceptor ribbon synapses involve the immunoglobulin protein synaptic cell adhesion molecule 1.

    PubMed

    Ribic, Adema; Liu, Xinran; Crair, Michael C; Biederer, Thomas

    2014-03-01

    Adhesive interactions in the retina instruct the developmental specification of inner retinal layers. However, potential roles of adhesion in the development and function of photoreceptor synapses remain incompletely understood. This contrasts with our understanding of synapse development in the CNS, which can be guided by select adhesion molecules such as the Synaptic Cell Adhesion Molecule 1 (SynCAM 1/CADM1/nectin-like 2 protein). This immunoglobulin superfamily protein modulates the development and plasticity of classical excitatory synapses. We show here by immunoelectron microscopy and immunoblotting that SynCAM 1 is expressed on mouse rod photoreceptors and their terminals in the outer nuclear and plexiform layers in a developmentally regulated manner. Expression of SynCAM 1 on rods is low in early postnatal stages (P3-P7) but increases after eye opening (P14). In support of functional roles in the photoreceptors, electroretinogram recordings demonstrate impaired responses to light stimulation in SynCAM 1 knockout (KO) mice. In addition, the structural integrity of synapses in the OPL requires SynCAM 1. Quantitative ultrastructural analysis of SynCAM 1 KO retina measured fewer fully assembled, triadic rod ribbon synapses. Furthermore, rod synapse ribbons are shortened in KO mice, and protein levels of Ribeye, a major structural component of ribbons, are reduced in SynCAM 1 KO retina. Together, our results implicate SynCAM 1 in the synaptic organization of the rod visual pathway and provide evidence for novel roles of synaptic adhesion in the structural and functional integrity of ribbon synapses.

  20. High soluble vascular cell adhesion molecule-1 concentrations predict long-term mortality in hemodialysis patients.

    PubMed

    Chang, Jia-Feng; Hsu, Shih-Ping; Pai, Mei-Fen; Yang, Ju-Yeh; Chen, Hung-Yuan; Wu, Hon-Yen; Peng, Yu-Sen

    2013-12-01

    Soluble vascular cell adhesion molecule-1 (sVCAM-1) has a strong association with cardiovascular deaths in patients with coronary artery disease. The aim of this study is to explore the association between sVCAM-1 and cardiovascular mortality in maintenance hemodialysis (MHD) patients. Eighty-three clinically stable MHD patients (mean age of 59.4 ± 13.7 years) at a single hospital-based dialysis facility were included. sVCAM-1, soluble intercellular adhesion molecule-1 (sICAM-1), and soluble E-selectin (sE-selectin) were determined at study baseline. The study cohort was divided into higher and lower concentration groups by the median value. The all-cause and cardiovascular mortality of this cohort were followed for 7 years. The mean concentrations of sVCAM-1, sICAM-1, and sE-selectin were 1,393.08 ± 300.96, 230.16 ± 84.86, and 60.01 ± 42.00 ng/mL, respectively. The higher concentration groups of sVCAM-1 and sICAM-1 had higher all-cause mortality by Kaplan-Meier analysis (p = 0.002 and p = 0.030, respectively). Higher sVCAM-1 concentrations had a higher risk of all-cause and cardiovascular mortality (p = 0.006 p = 0.046, respectively) in Cox proportional hazards model analysis. In MHD patients, higher sVCAM-1 concentrations independently predict all-cause and cardiovascular mortality. This biomarker may be used as a valid surrogate marker for predicting outcomes.

  1. Clinical significance of circulating vascular cell adhesion molecule-1 to white matter disintegrity in Alzheimer's dementia.

    PubMed

    Huang, Chi-Wei; Tsai, Meng-Han; Chen, Nai-Ching; Chen, Wei-Hsi; Lu, Yan-Ting; Lui, Chun-Chung; Chang, Ya-Ting; Chang, Wen-Neng; Chang, Alice Y W; Chang, Chiung-Chih

    2015-11-25

    Endothelial dysfunction leads to worse cognitive performance in Alzheimer's dementia (AD). While both cerebrovascular risk factors and endothelial dysfunction lead to activation of vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and E-selectin, it is not known whether these biomarkers extend the diagnostic repertoire in reflecting intracerebral structural damage or cognitive performance. A total of 110 AD patients and 50 age-matched controls were enrolled. Plasma levels of VCAM-1, ICAM-1 and E-selectin were measured and correlated with the cognitive performance, white matter macro-structural changes, and major tract-specific fractional anisotropy quantification. The AD patients were further stratified by clinical dementia rating score (mild dementia, n=60; moderate-to-severe dementia, n=50). Compared with the controls, plasma levels of VCAM-1 (p< 0.001), ICAM-1 (p=0.028) and E-selectin (p=0.016) were significantly higher in the patients, but only VCAM-1 levels significantly reflected the severity of dementia (p< 0.001). In addition, only VCAM-1 levels showed an association with macro- and micro- white matter changes especially in the superior longitudinal fasciculus (p< 0.001), posterior thalamic radiation (p=0.002), stria terminalis (p=0.002) and corpus callosum (p=0.009), and were independent of, age and cortical volume. These tracts show significant association with MMSE, short term memory and visuospatial function. Meanwhile, while VCAM-1 level correlated significantly with short-term memory (p=0.026) and drawing (p=0.025) scores in the AD patients after adjusting for age and education, the significance disappeared after adjusting for global FA. Endothelial activation, especially VCAM-1, was of clinical significance in AD that reflects macro- and micro-structural changes and poor short term memory and visuospatial function.

  2. Role of intercellular adhesion molecule 1 in pathogenesis of staphylococcal arthritis and in host defense against staphylococcal bacteremia.

    PubMed Central

    Verdrengh, M; Springer, T A; Gutierrez-Ramos, J C; Tarkowski, A

    1996-01-01

    Intercellular adhesion molecule 1 (ICAM-1) is a member of the immunoglobulin superfamily that interacts with two integrins, LFA-1 and Mac-1. These interactions are critical for leukocyte extravasation into inflamed tissue. To assess the role of ICAM-1 expression in the pathogenesis of bacterial infection, homozygously mutant mice lacking the ICAM-1 gene were exposed to Staphylococcus aureus. Within 6 days after inoculation 50% of the animals in the ICAM-1(-/-) group, but none of the controls, had died. Despite the high level of mortality, ICAM-1(-/-) mice developed less frequent and less severe arthritis than their wild-type littermates. In agreement, normal mice inoculated with staphylococci and administered anti-ICAM-1 antibodies exhibited a higher frequency of mortality but less severe arthritis than the controls. Our results indicate that ICAM-1 on the one hand provides protection against systemic disease but on the other hand aggravates the local disease manifestation. PMID:8698512

  3. Intercellular adhesion molecule-1: a consistent inflammatory marker of the cutaneous radiation reaction both in vitro and in vivo.

    PubMed

    Müller, K; Köhn, F-M; Port, M; Abend, M; Molls, M; Ring, J; Meineke, V

    2006-10-01

    Radiation damage to skin is a key diagnostic and prognostic parameter for patients accidentally exposed to radiation. Moreover, skin is a target organ for crucial side-effects of routine radiotherapy. The pathophysiology of the cutaneous radiation reaction is in many respects still unknown. The acute inflammatory radiation reaction of skin has been shown to involve alterations in cell-cell and cell-matrix interactions, which are mediated by cellular adhesion molecules. To evaluate the effect of ionizing radiation on intercellular adhesion molecule-1 (ICAM-1) expression in human skin cells. Dermal monolayer cells, a three-dimensional skin model and skin biopsies were investigated for ICAM-1 expression after ionizing radiation using flow cytometry, quantitative reverse transcription-polymerase chain reaction and immunohistochemistry. ICAM-1 expression in monolayer cells pretreated with protein kinase inhibitors and dexamethasone prior to irradiation was analysed by flow cytometry. Using different sources of skin cells, we demonstrated a consistent upregulation of both ICAM-1 mRNA and protein expression by ionizing radiation. Blocking experiments revealed that tumour necrosis factor-alpha, another ICAM-1 inducer, does not account for the effect of radiation. Radiation-induced upregulation of ICAM-1 expression was significantly attenuated by inhibitors to protein kinase C, mitogen-activated protein (MAP) ERK kinase, p38 MAP kinase and phosphatidylinositol 3-kinase. The anti-inflammatory agent dexamethasone suppressed the effect of radiation on ICAM-1 expression, suggesting its usefulness to treat the cutaneous radiation reaction. Our data suggest that ICAM-1 is a consistent inflammatory parameter of the cutaneous radiation reaction both in vitro and in vivo that might provide new therapeutic options for diagnosis and treatment of effects of radiation.

  4. The Prion Protein Controls Polysialylation of Neural Cell Adhesion Molecule 1 during Cellular Morphogenesis

    PubMed Central

    Mehrabian, Mohadeseh; Brethour, Dylan; Wang, Hansen; Xi, Zhengrui; Rogaeva, Ekaterina; Schmitt-Ulms, Gerold

    2015-01-01

    Despite its multi-faceted role in neurodegenerative diseases, the physiological function of the prion protein (PrP) has remained elusive. On the basis of its evolutionary relationship to ZIP metal ion transporters, we considered that PrP may contribute to the morphogenetic reprogramming of cells underlying epithelial-to-mesenchymal transitions (EMT). Consistent with this hypothesis, PrP transcription increased more than tenfold during EMT, and stable PrP-deficient cells failed to complete EMT in a mammalian cell model. A global comparative proteomics analysis identified the neural cell adhesion molecule 1 (NCAM1) as a candidate mediator of this impairment, which led to the observation that PrP-deficient cells fail to undergo NCAM1 polysialylation during EMT. Surprisingly, this defect was caused by a perturbed transcription of the polysialyltransferase ST8SIA2 gene. Proteomics data pointed toward β-catenin as a transcriptional regulator affected in PrP-deficient cells. Indeed, pharmacological blockade or siRNA-based knockdown of β-catenin mimicked PrP-deficiency in regards to NCAM1 polysialylation. Our data established the existence of a PrP-ST8SIA2-NCAM signaling loop, merged two mature fields of investigation and offer a simple model for explaining phenotypes linked to PrP. PMID:26288071

  5. Reduced Hepatic Carcinoembryonic Antigen-Related Cell Adhesion Molecule 1 Level in Obesity

    PubMed Central

    Heinrich, Garrett; Muturi, Harrison T.; Rezaei, Khadijeh; Al-Share, Qusai Y.; DeAngelis, Anthony M.; Bowman, Thomas A.; Ghadieh, Hilda E.; Ghanem, Simona S.; Zhang, Deqiang; Garofalo, Robert S.; Yin, Lei; Najjar, Sonia M.

    2017-01-01

    Impairment of insulin clearance is being increasingly recognized as a critical step in the development of insulin resistance and metabolic disease. The carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) promotes insulin clearance. Null deletion or liver-specific inactivation of Ceacam1 in mice causes a defect in insulin clearance, insulin resistance, steatohepatitis, and visceral obesity. Immunohistological analysis revealed reduction of hepatic CEACAM1 in obese subjects with fatty liver disease. Thus, we aimed to determine whether this occurs at the hepatocyte level in response to systemic extrahepatic factors and whether this holds across species. Northern and Western blot analyses demonstrate that CEACAM1 mRNA and protein levels are reduced in liver tissues of obese individuals compared to their lean age-matched counterparts. Furthermore, Western analysis reveals a comparable reduction of CEACAM1 protein in primary hepatocytes derived from the same obese subjects. Similar to humans, Ceacam1 mRNA level, assessed by quantitative RT-PCR analysis, is significantly reduced in the livers of obese Zucker (fa/fa, ZDF) and Koletsky (f/f) rats relative to their age-matched lean counterparts. These studies demonstrate that the reduction of hepatic CEACAM1 in obesity occurs at the level of hepatocytes and identify the reduction of hepatic CEACAM1 as a common denominator of obesity across multiple species. PMID:28396653

  6. The Prion Protein Controls Polysialylation of Neural Cell Adhesion Molecule 1 during Cellular Morphogenesis.

    PubMed

    Mehrabian, Mohadeseh; Brethour, Dylan; Wang, Hansen; Xi, Zhengrui; Rogaeva, Ekaterina; Schmitt-Ulms, Gerold

    2015-01-01

    Despite its multi-faceted role in neurodegenerative diseases, the physiological function of the prion protein (PrP) has remained elusive. On the basis of its evolutionary relationship to ZIP metal ion transporters, we considered that PrP may contribute to the morphogenetic reprogramming of cells underlying epithelial-to-mesenchymal transitions (EMT). Consistent with this hypothesis, PrP transcription increased more than tenfold during EMT, and stable PrP-deficient cells failed to complete EMT in a mammalian cell model. A global comparative proteomics analysis identified the neural cell adhesion molecule 1 (NCAM1) as a candidate mediator of this impairment, which led to the observation that PrP-deficient cells fail to undergo NCAM1 polysialylation during EMT. Surprisingly, this defect was caused by a perturbed transcription of the polysialyltransferase ST8SIA2 gene. Proteomics data pointed toward β-catenin as a transcriptional regulator affected in PrP-deficient cells. Indeed, pharmacological blockade or siRNA-based knockdown of β-catenin mimicked PrP-deficiency in regards to NCAM1 polysialylation. Our data established the existence of a PrP-ST8SIA2-NCAM signaling loop, merged two mature fields of investigation and offer a simple model for explaining phenotypes linked to PrP.

  7. Soluble intercellular adhesion molecule-1: a potential biomarker for pain intensity in chronic pain patients.

    PubMed

    Luchting, Benjamin; Hinske, Ludwig Christian Giuseppe; Rachinger-Adam, Banafscheh; Celi, Leo Anthony; Kreth, Simone; Azad, Shahnaz Christina

    2017-03-01

    Pain therapy is strongly guided by patients' self-reporting. However, when self-reporting is not an option, pain assessment becomes a challenge and may lead to undertreatment of painful conditions. Pain is a complex and multifactorial phenomenon. Recent work has connected pain pathophysiology also with the inflammatory system. We therefore hypothesized that pain intensity could be predicted by cytokine-levels. In this observational, single-center study, we investigated 30 serum cytokines to predict pain intensity in a screening/follow-up set of 95 chronic pain patients and controls. We then prospectively validated soluble intercellular adhesion molecule-1 (sICAM-1)'s discriminatory capability (n = 21). sICAM-1 was significantly associated with patient-reported pain intensity and yielded differential serum levels in patients of varying degrees of pain intensity. Changes in pain ratings over time correlated with changes in sICAM-1 levels. Our findings suggest the possibility of a clinical use of sICAM-1 as a potential biomarker for pain intensity.

  8. Polymorphisms in the intercellular adhesion molecule 1 gene and cancer risk: a meta-analysis

    PubMed Central

    Tang, Weifeng; Wang, Yafeng; Chen, Yuanmei; Gu, Haiyong; Chen, Shuchen; Kang, Mingqiang

    2015-01-01

    Objectives: The correlation between intercellular adhesion molecule 1 (ICAM-1) common polymorphisms (rs5498 A>G and rs3093030 C>T) and cancer susceptibility has been explored in various ethnic groups and different cancer types; however, these investigations have yielded contradictory results. To address the relationship more precisely, we performed this meta-analysis. Design and methods: EmBase, PubMed and China National Knowledge Infrastructure (CNKI) databases were searched by two authors independently for eligible publications before April 8, 2015. Random-effects or fixed-effects model was harnessed to calculate the pooled odds ratios (ORs) and 95% confidence intervals (CIs) when appropriate. Results: The result suggested that the ICAM-1 rs5498 A>G polymorphism is not associated with cancer susceptibility in overall cancer. In a stratified analysis by ethnicity, a significant increased cancer risk was identified among Asians, but the inverse association was found among Caucasians. In a stratified analysis by cancer type, ICAM-1 rs5498 A>G polymorphism was associated with a significantly increased risk of oral cancer, but with protection from colorectal cancer and melanoma. ICAM-1 rs3093030 C>T polymorphism is not correlated with cancer susceptibility. Conclusions: In summary, this meta-analysis highlights that the ICAM-1 rs5498 A>G polymorphism probably contributes to decreased susceptibility to cancer, especially in Caucasians, in melanoma and colorectal cancer subgroup, but it may be a risk factor for oral cancer and Asians. PMID:26550112

  9. Reduced Hepatic Carcinoembryonic Antigen-Related Cell Adhesion Molecule 1 Level in Obesity.

    PubMed

    Heinrich, Garrett; Muturi, Harrison T; Rezaei, Khadijeh; Al-Share, Qusai Y; DeAngelis, Anthony M; Bowman, Thomas A; Ghadieh, Hilda E; Ghanem, Simona S; Zhang, Deqiang; Garofalo, Robert S; Yin, Lei; Najjar, Sonia M

    2017-01-01

    Impairment of insulin clearance is being increasingly recognized as a critical step in the development of insulin resistance and metabolic disease. The carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) promotes insulin clearance. Null deletion or liver-specific inactivation of Ceacam1 in mice causes a defect in insulin clearance, insulin resistance, steatohepatitis, and visceral obesity. Immunohistological analysis revealed reduction of hepatic CEACAM1 in obese subjects with fatty liver disease. Thus, we aimed to determine whether this occurs at the hepatocyte level in response to systemic extrahepatic factors and whether this holds across species. Northern and Western blot analyses demonstrate that CEACAM1 mRNA and protein levels are reduced in liver tissues of obese individuals compared to their lean age-matched counterparts. Furthermore, Western analysis reveals a comparable reduction of CEACAM1 protein in primary hepatocytes derived from the same obese subjects. Similar to humans, Ceacam1 mRNA level, assessed by quantitative RT-PCR analysis, is significantly reduced in the livers of obese Zucker (fa/fa, ZDF) and Koletsky (f/f) rats relative to their age-matched lean counterparts. These studies demonstrate that the reduction of hepatic CEACAM1 in obesity occurs at the level of hepatocytes and identify the reduction of hepatic CEACAM1 as a common denominator of obesity across multiple species.

  10. Mechanism of Collaborative Enhancement of Binding of Paired Antibodies to Distinct Epitopes of Platelet Endothelial Cell Adhesion Molecule-1

    PubMed Central

    Greineder, Colin F.; Villa, Carlos H.; Hood, Elizabeth D.; Shuvaev, Vladimir V.; Sun, Jing; Chacko, Ann-Marie; Abraham, Valsamma; DeLisser, Horace M.; Muzykantov, Vladimir R.

    2017-01-01

    Monoclonal antibodies (mAbs) directed to extracellular epitopes of human and mouse Platelet Endothelial Cell Adhesion Molecule-1 (CD31 or PECAM-1) stimulate binding of other mAbs to distinct adjacent PECAM-1 epitopes. This effect, dubbed Collaborative Enhancement of Paired Affinity Ligands, or CEPAL, has been shown to enhance delivery of mAb-targeted drugs and nanoparticles to the vascular endothelium. Here we report new insights into the mechanism underlying this effect, which demonstrates equivalent amplitude in the following models: i) cells expressing a full length PECAM-1 and mutant form of PECAM-1 unable to form homodimers; ii) isolated fractions of cellular membranes; and, iii) immobilized recombinant PECAM-1. These results indicate that CEPAL is mediated not by interference in cellular functions or homophilic PECAM-1 interactions, but rather by conformational changes within the cell adhesion molecule induced by ligand binding. This mechanism, mediated by exposure of partially occult epitopes, is likely to occur in molecules other than PECAM-1 and may represent a generalizable phenomenon with valuable practical applications. PMID:28085903

  11. Mechanism of Collaborative Enhancement of Binding of Paired Antibodies to Distinct Epitopes of Platelet Endothelial Cell Adhesion Molecule-1.

    PubMed

    Kiseleva, Raisa; Greineder, Colin F; Villa, Carlos H; Hood, Elizabeth D; Shuvaev, Vladimir V; Sun, Jing; Chacko, Ann-Marie; Abraham, Valsamma; DeLisser, Horace M; Muzykantov, Vladimir R

    2017-01-01

    Monoclonal antibodies (mAbs) directed to extracellular epitopes of human and mouse Platelet Endothelial Cell Adhesion Molecule-1 (CD31 or PECAM-1) stimulate binding of other mAbs to distinct adjacent PECAM-1 epitopes. This effect, dubbed Collaborative Enhancement of Paired Affinity Ligands, or CEPAL, has been shown to enhance delivery of mAb-targeted drugs and nanoparticles to the vascular endothelium. Here we report new insights into the mechanism underlying this effect, which demonstrates equivalent amplitude in the following models: i) cells expressing a full length PECAM-1 and mutant form of PECAM-1 unable to form homodimers; ii) isolated fractions of cellular membranes; and, iii) immobilized recombinant PECAM-1. These results indicate that CEPAL is mediated not by interference in cellular functions or homophilic PECAM-1 interactions, but rather by conformational changes within the cell adhesion molecule induced by ligand binding. This mechanism, mediated by exposure of partially occult epitopes, is likely to occur in molecules other than PECAM-1 and may represent a generalizable phenomenon with valuable practical applications.

  12. Identification of Human Junctional Adhesion Molecule 1 as a Functional Receptor for the Hom-1 Calicivirus on Human Cells

    PubMed Central

    Sandoval-Jaime, Carlos; Parra, Gabriel I.; Tin, Christine M.; Jones, Ronald W.; Soden, Jo; Barnes, Donna; Freeth, Jim; Smith, Alvin W.; Green, Kim Y.

    2017-01-01

    ABSTRACT The Hom-1 vesivirus was reported in 1998 following the inadvertent transmission of the animal calicivirus San Miguel sea lion virus to a human host in a laboratory. We characterized the Hom-1 strain and investigated the mechanism by which human cells could be infected. An expression library of 3,559 human plasma membrane proteins was screened for reactivity with Hom-1 virus-like particles, and a single interacting protein, human junctional adhesion molecule 1 (hJAM1), was identified. Transient expression of hJAM1 conferred susceptibility to Hom-1 infection on nonpermissive Chinese hamster ovary (CHO) cells. Virus infection was markedly inhibited when CHO cells stably expressing hJAM were pretreated with anti-hJAM1 monoclonal antibodies. Cell lines of human origin were tested for growth of Hom-1, and efficient replication was observed in HepG2, HuH7, and SK-CO15 cells. The three cell lines (of hepatic or intestinal origin) were confirmed to express hJAM1 on their surface, and clustered regularly interspaced short palindromic repeats/Cas9-mediated knockout of the hJAM1 gene in each line abolished Hom-1 propagation. Taken together, our data indicate that entry of the Hom-1 vesivirus into these permissive human cell lines is mediated by the plasma membrane protein hJAM1 as a functional receptor. PMID:28196955

  13. Identification of Human Junctional Adhesion Molecule 1 as a Functional Receptor for the Hom-1 Calicivirus on Human Cells.

    PubMed

    Sosnovtsev, Stanislav V; Sandoval-Jaime, Carlos; Parra, Gabriel I; Tin, Christine M; Jones, Ronald W; Soden, Jo; Barnes, Donna; Freeth, Jim; Smith, Alvin W; Green, Kim Y

    2017-02-14

    The Hom-1 vesivirus was reported in 1998 following the inadvertent transmission of the animal calicivirus San Miguel sea lion virus to a human host in a laboratory. We characterized the Hom-1 strain and investigated the mechanism by which human cells could be infected. An expression library of 3,559 human plasma membrane proteins was screened for reactivity with Hom-1 virus-like particles, and a single interacting protein, human junctional adhesion molecule 1 (hJAM1), was identified. Transient expression of hJAM1 conferred susceptibility to Hom-1 infection on nonpermissive Chinese hamster ovary (CHO) cells. Virus infection was markedly inhibited when CHO cells stably expressing hJAM were pretreated with anti-hJAM1 monoclonal antibodies. Cell lines of human origin were tested for growth of Hom-1, and efficient replication was observed in HepG2, HuH7, and SK-CO15 cells. The three cell lines (of hepatic or intestinal origin) were confirmed to express hJAM1 on their surface, and clustered regularly interspaced short palindromic repeats/Cas9-mediated knockout of the hJAM1 gene in each line abolished Hom-1 propagation. Taken together, our data indicate that entry of the Hom-1 vesivirus into these permissive human cell lines is mediated by the plasma membrane protein hJAM1 as a functional receptor.IMPORTANCE Vesiviruses, such as San Miguel sea lion virus and feline calicivirus, are typically associated with infection in animal hosts. Following the accidental infection of a laboratory worker with San Miguel sea lion virus, a related virus was isolated in cell culture and named Hom-1. In this study, we found that Hom-1 could be propagated in a number of human cell lines, making it the first calicivirus to replicate efficiently in cultured human cells. Screening of a library of human cell surface membrane proteins showed that the virus could utilize human junctional adhesion molecule 1 as a receptor to enter cells and initiate replication. The Hom-1 virus presents a new

  14. Clinical Significance of Soluble Intercellular Adhesion Molecule-1 and Interleukin-6 in Patients with Extrahepatic Cholangiocarcinoma.

    PubMed

    Shimura, Tatsuo; Shibata, Masahiko; Gonda, Kenji; Kofunato, Yasuhide; Okada, Ryo; Ishigame, Teruhide; Kimura, Takashi; Kenjo, Akira; Marubashi, Shigeru; Kono, Koji; Takenoshita, Seiichi

    2017-09-19

    Purpose/Aim: Although several prognostic factors for extrahepatic cholangiocarcinoma (EHC) have been reported, preoperative prognostic factors have yet to be established. We investigated the serum concentration of angiogenic, inflammatory, and nutritional parameters. Twenty-five patients with EHC were enrolled before starting treatment. Preoperative prognostic factors were identified using multivariate analyses. The serum soluble intercellular adhesion molecule-1 (sICAM-1) levels were significantly higher in the patients with EHC (436.0 ± 43.2 ng/ml) than in the healthy volunteers (228.6 ± 22.0 ng/ml) (p <.001). In addition, the serum IL-6 levels were significantly higher in the patients (18.0 ± 5.6 pg/ml) than in the healthy volunteers (5.7 ± 0.8 pg/ml) (p <.05). The serum IL-6 and sICAM-1 showed a strong correlation (r = 0.559) in the patients with EHC (p <.01). The serum IL-6 (area under the curve = 0.764, p =.030, cut-off level = 11.6) and sICAM-1 (area under the curve = 0.818, p =.007, cutoff level = 322.6) were revealed to be useful as prognostic factors by the receiver operating characteristic curves. The high IL-6 group and the high sICAM-1 group showed poorer DSS than those of the respective low groups. In the multivariate analysis, IL-6 (hazard ratio: 1.050, 95% confidence interval: 1.002-1.100, p =.043) and sICAM-1 (hazard ratio: 1.009, 95% confidence interval: 1.002-1.015, p =.009) were independent prognostic factors for DSS. IL-6 and sICAM-1 were independent preoperative prognostic factors in EHC patients, causing continuous inflammation and malnutrition in collaboration with other pro-angiogenic factors.

  15. Cannabidiol inhibits lung cancer cell invasion and metastasis via intercellular adhesion molecule-1.

    PubMed

    Ramer, Robert; Bublitz, Katharina; Freimuth, Nadine; Merkord, Jutta; Rohde, Helga; Haustein, Maria; Borchert, Philipp; Schmuhl, Ellen; Linnebacher, Michael; Hinz, Burkhard

    2012-04-01

    Cannabinoids inhibit cancer cell invasion via increasing tissue inhibitor of matrix metalloproteinases-1 (TIMP-1). This study investigates the role of intercellular adhesion molecule-1 (ICAM-1) within this action. In the lung cancer cell lines A549, H358, and H460, cannabidiol (CBD; 0.001-3 μM) elicited concentration-dependent ICAM-1 up-regulation compared to vehicle via cannabinoid receptors, transient receptor potential vanilloid 1, and p42/44 mitogen-activated protein kinase. Up-regulation of ICAM-1 mRNA by CBD in A549 was 4-fold at 3 μM, with significant effects already evident at 0.01 μM. ICAM-1 induction became significant after 2 h, whereas significant TIMP-1 mRNA increases were observed only after 48 h. Inhibition of ICAM-1 by antibody or siRNA approaches reversed the anti-invasive and TIMP-1-upregulating action of CBD and the likewise ICAM-1-inducing cannabinoids Δ(9)-tetrahydrocannabinol and R(+)-methanandamide when compared to isotype or nonsilencing siRNA controls. ICAM-1-dependent anti-invasive cannabinoid effects were confirmed in primary tumor cells from a lung cancer patient. In athymic nude mice, CBD elicited a 2.6- and 3.0-fold increase of ICAM-1 and TIMP-1 protein in A549 xenografts, as compared to vehicle-treated animals, and an antimetastatic effect that was fully reversed by a neutralizing antibody against ICAM-1 [% metastatic lung nodules vs. isotype control (100%): 47.7% for CBD + isotype antibody and 106.6% for CBD + ICAM-1 antibody]. Overall, our data indicate that cannabinoids induce ICAM-1, thereby conferring TIMP-1 induction and subsequent decreased cancer cell invasiveness.

  16. Intercellular Adhesion Molecule-1 (ICAM-1) Polymorphisms and Cancer Risk: A Meta-Analysis

    PubMed Central

    CHENG, Daye; LIANG, Bin

    2015-01-01

    Background: Intercellular adhesion molecule-1 (ICAM-1) Lys469Glu (K469E) polymorphism and Gly 241Arg (G241R) polymorphism might play important roles in cancer development and progression. However, the results of previous studies are inconsistent. The aim of this study was to evaluate the association between ICAM-1 K469E and G241R polymorphisms and the risk of cancer by meta-analysis. Methods: A comprehensive literature search (last search updated in November 2013) was conducted to identify case-control studies that investigated the association between ICAM-1 K469E and G241R polymorphisms and cancer risk. Results: A total of 18 case-control studies for ICAM-1 polymorphisms were included in the meta-analysis, including 4,844 cancer cases and 5,618 healthy controls. For K469E polymorphism, no significant association was found between K469E polymorphism and cancer risk. However, subgroup analysis by ethnicity revealed one genetic comparison (GG vs. AA) presented the relationship with cancer risk in Asian subgroup, and two genetic models (GG+GA vs. AA and GA vs. AA) in European subgroup, respectively. For G241R polymorphism, G241R polymorphism was significantly association with cancer risk in overall analysis. The subgroup analysis by ethnicity showed that G241R polymorphism was significantly associated with cancer risk in European subgroup. Conclusion: ICAM-1 G241R polymorphism might be associated with cancer risk, especially in European populations, but the results doesn’t support ICAM-1 K469E polymorphism as a risk factor for cancer. PMID:26284202

  17. Intraocular soluble intracellular adhesion molecule-1 correlates with subretinal fluid height of diabetic macular edema

    PubMed Central

    Zhu, Dan; Zhu, He; Wang, Chunyan; Yang, Dayong

    2014-01-01

    Objective: To investigate the correlations between aqueous concentrations of vascular endothelial growth factor (VEGF), monocyte chemoattractant protein-1 (MCP-1), soluble intracellular adhesion molecule-1 (sICAM-1) and diabetic macular edema (DME). Materials and Methods: VEGF, MCP-1 and sICAM-1 concentrations in aqueous humor samples of 22 patients with DME and 23 patients with cataract of a control group were measured with solid-phase chemiluminescence immunoassay. Results: Aqueous VEGF (89.2 ± 58.5 pg/ml versus 48.5 ± 27.8 pg/ml, P = 0.006), MCP-1 (684.2 ± 423.4 pg/ml versus 432.4 ± 230.4 pg/ml, P = 0.019) and sICAM-1 (3213.8 ± 2581.6 pg/ml versus 260.2 ± 212.2 pg/ml, P < 0.001) all vary significantly between DME group and control group. Maximum height of submacular fluid measured by Optical coherence tomography (OCT) was significantly associated with aqueous sICAM-1 (r = -0.45, P = 0.034). The maximum height of macular thickness measured by OCT was not significantly associated with either VEGF (P = 0.300), MCP-1 (P = 0.320) or sICAM-1 (P = 0.285). Conclusions: Our results suggest that sICAM-1 may majorly contribute to the formation of subretinal fluid in DME patients and imply that MCP-1 and sICAM-1 may be the potential therapy targets, besides VEGF. PMID:23619489

  18. Leukocytosis and resistance to septic shock in intercellular adhesion molecule 1-deficient mice

    PubMed Central

    1994-01-01

    Intercellular adhesion molecule 1 (ICAM-1) is one of three immunoglobulin superfamily members that bind to the integrins lymphocyte function associated 1 (LFA-1) and Mac-1 on leukocytes. We have generated mice that are genetically and functionally deficient in ICAM-1. These mice have elevated numbers of circulating neutrophils and lymphocytes, as well as diminished allogeneic T cell responses and delayed type hypersensitivity. Mutant mice are resistant to lethal effects of high doses of endotoxin (lipopolysaccharide [LPS]), and this correlates with a significant decrease in neutrophil infiltration in the liver. Production of inflammatory cytokines such as tumor necrosis factor alpha or interleukin 1 is normal in ICAM-1-deficient mice, and thus protection appears to be related to a diminution in critical leukocyte-endothelial interactions. After sensitization with D- galactosamine (D-Gal), ICAM-1-deficient mice are resistant to the lethal effect of low doses of exotoxin (Staphylococcus aureus enterotoxin B [SEB]), which has been shown to mediate its toxic effects via the activation of specific T cells. In this model, ICAM-1-mediated protection against SEB lethality correlates with a decrease in the systemic release of inflammatory cytokines, as well as with prevention of extensive hepatocyte necrosis and hemorrhage. ICAM-1-deficient mice sensitized with D-Gal, however, are not protected from lethality when challenged with low doses of endotoxin (LPS). These studies show that the different contribution of ICAM-1 in the activation of either T cells or macrophages is decisive for the fatal outcome of the shock in these two models. This work suggests that anti-ICAM-1 therapy may be beneficial in both gram-positive and -negative septic shock, either by reducing T cell activation or by diminishing neutrophil infiltration. PMID:7911822

  19. Targeted disruption of carcinoembryonic antigen-related cell adhesion molecule 1 promotes diet-induced hepatic steatosis and insulin resistance.

    PubMed

    Xu, Elaine; Dubois, Marie-Julie; Leung, Nelly; Charbonneau, Alexandre; Turbide, Claire; Avramoglu, Rita Kohen; DeMarte, Luisa; Elchebly, Mounib; Streichert, Thomas; Lévy, Emile; Beauchemin, Nicole; Marette, André

    2009-08-01

    Carcinoembryonic antigen-related cell adhesion molecule 1 (CC1) is a cell adhesion molecule within the Ig superfamily. The Tyr-phosphorylated isoform of CC1 (CC1-L) plays an important metabolic role in the regulation of hepatic insulin clearance. In this report, we show that CC1-deficient (Cc1(-/-)) mice are prone to hepatic steatosis, as revealed by significantly elevated hepatic triglyceride and both total and esterified cholesterol levels compared with age-matched wild-type controls. Cc1(-/-) mice were also predisposed to lipid-induced hepatic steatosis and dysfunction as indicated by their greater susceptibility to store lipids and express elevated levels of enzymatic markers of liver damage after chronic feeding of a high-fat diet. Hepatic steatosis in the Cc1(-/-) mice was linked to a significant increase in the expression of key lipogenic (fatty acid synthase, acetyl CoA carboxylase) and cholesterol synthetic (3-hydroxy-3-methylglutaryl-coenzyme A reductase) enzymes under the control of sterol regulatory element binding proteins-1c and -2 transcription factors. Cc1(-/-) mice also exhibited impaired insulin clearance, glucose intolerance, liver insulin resistance, and elevated hepatic expression of the key gluconeogenic transcriptional activators peroxisome proliferator-activated receptor-gamma coactivator-1 and Forkhead box O1. Lack of CC1 also exacerbated both glucose intolerance and hepatic insulin resistance induced by high-fat feeding, but insulin clearance was not further deteriorated in the high-fat-fed Cc1(-/-) mice. In conclusion, our data indicate that CC1 is a key regulator of hepatic lipogenesis and that Cc1(-/-) mice are predisposed to liver steatosis, leading to hepatic insulin resistance and liver damage, particularly when chronically exposed to dietary fat.

  20. SNPs in the neural cell adhesion molecule 1 gene (NCAM1) may be associated with human neural tube defects

    PubMed Central

    Deak, Kristen L.; Boyles, Abee L.; Etchevers, Heather C.; Melvin, Elizabeth C.; Siegel, Deborah G.; Graham, Felicia L.; Slifer, Susan H.; Enterline, David S.; George, Timothy M.; Vekemans, Michel; McClay, David; Bassuk, Alexander G.; Kessler, John A.; Linney, Elwood; Gilbert, John R.

    2011-01-01

    Neural tube defects (NTDs) are common birth defects, occurring in approximately 1/1,000 births; both genetic and environmental factors are implicated. To date, no major genetic risk factors have been identified. Throughout development, cell adhesion molecules are strongly implicated in cell–cell interactions, and may play a role in the formation and closure of the neural tube. To evaluate the role of neural cell adhesion molecule 1 (NCAM1) in risk of human NTDs, we screened for novel single-nucleotide polymorphisms (SNPs) within the gene. Eleven SNPs across NCAM1 were genotyped using TaqMan. We utilized a family-based approach to evaluate evidence for association and/or linkage disequilibrium. We evaluated American Caucasian simplex lumbosacral myelomeningocele families (n=132 families) using the family based association test (FBAT) and the pedigree disequilibrium test (PDT). Association analysis revealed a significant association between risk for NTDs and intronic SNP rs2298526 using both the FBAT test (P=0.0018) and the PDT (P=0.0025). Using the HBAT version of the FBAT to look for haplotype association, all pairwise comparisons with SNP rs2298526 were also significant. A replication study set, consisting of 72 additional families showed no significant association; however, the overall trend for overtransmission of the less common allele of SNP rs2298526 remained significant in the combined sample set. In addition, we analyzed the expression pattern of the NCAM1 protein in human embryos, and while NCAM1 is not expressed within the neural tube at the time of closure, it is expressed in the surrounding and later in differentiated neurons of the CNS. These results suggest variations in NCAM1 may influence risk for human NTDs. PMID:15883837

  1. Coexpression of intercellular adhesion molecule-1 and class I major histocompatibility complex antigens on hepatocyte membrane in chronic viral hepatitis.

    PubMed Central

    Chu, C M; Liaw, Y F

    1993-01-01

    AIMS--To evaluate the role of hepatocyte expression of leucocyte adhesion molecules and major histocompatibility complex (MHC) antigens in the pathogenesis of chronic viral hepatitis. METHODS--The expression of intercellular adhesion molecule 1 (ICAM-1), lymphocyte function associated antigen 3 (LFA-3), and MHC class I and II antigens on hepatocyte membrane in relation to the histological and biochemical activities was studied in patients with chronic B hepatitis, chronic persistent hepatitis (CPH) n = 23; chronic active hepatitis (CAH) n = 20; chronic D hepatitis (CAH) n = 6; and chronic non-A, non-B hepatitis (CPH n = 4, CAM n = 6). Six of the latter were hepatitis C virus antibody positive. RESULTS--In chronic B hepatitis ICAM-1 and MHC-I were expressed significantly more in patients with CAH than in those with CPH (p < 0.001), while the expression of LFA-3 and MHC-II showed no significant difference, irrespective of serum HBeAg or hepatitis B virus DNA. Similar findings were noted in non-A, non-B hepatitis. Regardless of the viral aetiology, patients with CAH had a significantly higher degree of ICAM-1 and MHC-I expression than LFA-3 (p < 0.001 v ICAM-1 and MHC-I, respectively) and MHC-II (p < 0.001 v ICAM-1 and MHC-I, respectively) expression. Those with CPH showed little or no difference in the expression of these four molecules. Furthermore, serum ALT values positively correlated with the hepatocyte expression of ICAM-1 (p < 0.001) and MHC-I (p < 0.001), but not LFA-3 (p > 0.05) and MHC-II (p > 0.05). CONCLUSIONS--In chronic viral hepatitis hepatocyte expression of ICAM-1 and MHC-I might be important for immunosurveillance against virally infected hepatocytes, while the expression of LFA-3 and MHC-II does not seem to have a role in the pathogenesis of chronic viral hepatitis. Images PMID:7902850

  2. Soluble Vascular Cell Adhesion Molecule-1 (VCAM-1) as a Biomarker in the Mouse Model of Experimental Autoimmune Myocarditis (EAM)

    PubMed Central

    Grabmaier, U.; Kania, G.; Kreiner, J.; Grabmeier, J.; Uhl, A.; Huber, B. C.; Lackermair, K.; Herbach, N.; Todica, A.; Eriksson, U.; Weckbach, L. T.; Brunner, S.

    2016-01-01

    Vascular cell adhesion molecule-1 (VCAM-1) is strongly upregulated in hearts of mice with coxsackie virus-induced as well as in patients with viral infection-triggered dilated cardiomyopathy. Nevertheless, the role of its soluble form as a biomarker in inflammatory heart diseases remains unclear. Therefore, we investigated whether plasma levels of soluble VCAM-1 (sVCAM-1) directly correlated with disease activity and progression of cardiac dysfunction in the mouse model of experimental autoimmune myocarditis (EAM). EAM was induced by immunization of BALB/c mice with heart-specific myosin-alpha heavy chain peptide together with complete Freund`s adjuvant. ELISA revealed strong expression of cardiac VCAM-1 (cVCAM-1) throughout the course of EAM in immunized mice compared to control animals. Furthermore, sVCAM-1 was elevated in the plasma of immunized compared to control mice at acute and chronic stages of the disease. sVCAM-1 did not correlate with the degree of acute cardiac inflammation analyzed by histology or cardiac cytokine expression investigated by ELISA. Nevertheless, heart to body weight ratio correlated significantly with sVCAM-1 at chronic stages of EAM. Cardiac systolic dysfunction studied with positron emission tomography indicated a weak relationship with sVCAM-1 at the chronic stage of the disease. Our data provide evidence that plasma levels of sVCAM-1 are elevated throughout all stages of the disease but showed no strong correlation with the severity of EAM. PMID:27501319

  3. Soluble fms-like tyrosine kinase-1 and endothelial adhesion molecules (intercellular cell adhesion molecule-1 and vascular cell adhesion molecule-1) as predictive markers for blood pressure reduction after renal sympathetic denervation.

    PubMed

    Dörr, Oliver; Liebetrau, Christoph; Möllmann, Helge; Gaede, Luise; Troidl, Christian; Rixe, Johannes; Hamm, Christian; Nef, Holger

    2014-05-01

    Renal sympathetic denervation (RSD) is a treatment option for patients with resistant arterial hypertension, but in some patients it is not successful. Predictive parameters on the success of RSD remain unknown. The angiogenic factors soluble fms-like tyrosine kinase-1 (sFLT-1), intercellular cell adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) are known to be associated with endothelial dysfunction, vascular remodeling, and hypertension. We evaluated whether sFLT-1, ICAM-1, and VCAM-1 are predictive markers for blood pressure reduction after RSD. Consecutive patients (n=55) undergoing renal denervation were included. Venous serum samples for measurement of sFlt-1, ICAM-1, and VCAM-1 were collected before and 6 months after RSD. A therapeutic response was defined as an office systolic blood pressure reduction of >10 mm Hg 6 months after RSD. A significant mean office systolic blood pressure reduction of 31.2 mm Hg was observed in 46 patients 6 months after RSD. Nine patients were classified as nonresponders, with a mean systolic blood pressure reduction of 4.6 mm Hg. At baseline, sFLT-1 levels were significantly higher in responders than in nonresponders (P<0.001) as were ICAM-1 (P<0.001) and VCAM-1 levels (P<0.01). The areas under the curve for sFLT-1, ICAM-1, and VCAM-1 were 0.82 (interquartile range, 0.718-0.921; P<0.001), 0.754 (0.654-0.854; P<0.001), and 0.684 (0.564-804; P=0.01), respectively, demonstrating prediction of an RSD response. Responders showed significantly higher serum levels of sFLT-1, ICAM-1, and VCAM-1 at baseline compared with nonresponders. Thus, this study identified for the first time potential biomarkers with a predictive value indicating a responder or nonresponder before renal denervation.

  4. Platelet endothelial cell adhesion molecule-1 mediates endothelial-cardiomyocyte communication and regulates cardiac function.

    PubMed

    McCormick, Margaret E; Collins, Caitlin; Makarewich, Catherine A; Chen, Zhongming; Rojas, Mauricio; Willis, Monte S; Houser, Steven R; Tzima, Ellie

    2015-01-19

    Dilated cardiomyopathy is characterized by impaired contractility of cardiomyocytes, ventricular chamber dilatation, and systolic dysfunction. Although mutations in genes expressed in the cardiomyocyte are the best described causes of reduced contractility, the importance of endothelial-cardiomyocyte communication for proper cardiac function is increasingly appreciated. In the present study, we investigate the role of the endothelial adhesion molecule platelet endothelial cell adhesion molecule (PECAM-1) in the regulation of cardiac function. Using cell culture and animal models, we show that PECAM-1 expressed in endothelial cells (ECs) regulates cardiomyocyte contractility and cardiac function via the neuregulin-ErbB signaling pathway. Conscious echocardiography revealed left ventricular (LV) chamber dilation and systolic dysfunction in PECAM-1(-/-) mice in the absence of histological abnormalities or defects in cardiac capillary density. Despite deficits in global cardiac function, cardiomyocytes isolated from PECAM-1(-/-) hearts displayed normal baseline and isoproterenol-stimulated contractility. Mechanistically, absence of PECAM-1 resulted in elevated NO/ROS signaling and NRG-1 release from ECs, which resulted in augmented phosphorylation of its receptor ErbB2. Treatment of cardiomyocytes with conditioned media from PECAM-1(-/-) ECs resulted in enhanced ErbB2 activation, which was normalized by pre-treatment with an NRG-1 blocking antibody. To determine whether normalization of increased NRG-1 levels could correct cardiac function, PECAM-1(-/-) mice were treated with the NRG-1 blocking antibody. Echocardiography showed that treatment significantly improved cardiac function of PECAM-1(-/-) mice, as revealed by increased ejection fraction and fractional shortening. We identify a novel role for PECAM-1 in regulating cardiac function via a paracrine NRG1-ErbB pathway. These data highlight the importance of tightly regulated cellular communication for proper

  5. FMC46, a cell protrusion-associated leukocyte adhesion molecule-1 epitope on human lymphocytes and thymocytes.

    PubMed

    Pilarski, L M; Turley, E A; Shaw, A R; Gallatin, W M; Laderoute, M P; Gillitzer, R; Beckman, I G; Zola, H

    1991-07-01

    In this report, we describe a 76-kDa glycoprotein recognized by mAb FMC46 that, by virtue of its concentration on cell protrusions involved in motility, may be important in lymphoid cell locomotion. FMC46 detects an epitope of the leukocyte adhesion molecule-1 (LAM-1), a member of the selecting family (LAM-1, Endothelial Leukocyte Adhesion Molecular-1 (ELAM-1), and Granule Membrane Protein-140 (GMP-140), that is expressed on LAM-1-transfected cell lines, is a glycosylation epitope based on its loss after culture in tunicamycin, and is closely related to the LAM-1.2 epitope. FMC46 is expressed at high density on the majority of CD45RA+ and CD45RO+ peripheral blood T cells (60 to 70%) and on a subset of thymocytes that includes the multinegative CD3- CD4- CD8- progenitor cells (100% FMC46hi) and the CD45R0- presumptive thymic generative lineage (70% FMC46hi). It appears at reduced density and frequency on CD45RA- thymocytes (50% FMC46lo), comprised mainly of death-committed thymocytes. Among thymic subsets defined by expression of CD4 and/or CD8, FMC46 is expressed at high density predominantly on a subset of single-positive cells and not on double-positive cells. These results suggest a fundamental role for LAM-1 in thymic development, with a high density preferentially expressed on cells involved in thymic generative processes and a low density on cells progressing to intrathymic death. A major subset of peripheral blood B cells and thymic B cells also express FMC46. Immunohistochemistry on frozen sections indicated strong staining in splenic follicles and around blood vessels, staining of the thymic medulla and subcapsular areas, and staining of the mantle zone of germinal centers of the lymph node. FMC46+ lymphocytes accumulated along high endothelial venules in the lymph node. On locomoting multinegative thymocytes, FMC46 is concentrated on the leading tip of extended processes, on pseudopods, and on ruffles, unlike the distribution of either CD44 or TQ1 (LAM 1

  6. Pentoxifylline inhibits intercellular adhesion molecule-1 (ICAM-1) and lung injury in experimental phosgene-exposure rats.

    PubMed

    Zhang, Xiao-di; Hou, Jun-Feng; Qin, Xu-Jun; Li, Wen-Li; Chen, Hong-Li; Liu, Rui; Liang, Xin; Hai, Chun-Xu

    2010-09-01

    Phosgene inhalation results in acute lung injury (ALI) mostly, pulmonary edema and even acute respiratory distress syndrome, but there is no specific antidote. Inflammatory cells play an important role in the ALI caused by phosgene. Intercellular adhesion molecule-1 (ICAM-1) is a critical factor for inflammatory organ injury. We hypothesized that pentoxifylline (PTX), an inhibitor of leukocyte activation, would have a protective effect on experimental phosgene-induced lung injury rats by inhibiting ICAM-1. To prove this hypothesis, we used rat models of phosgene (400 ppm x 1 min)-induced injury to investigate: (1) the time course of lung injury (control 1, 3, 6, 12, 24, and 48 h group), including pathological changes in hematoxylin and eosin staining and transmission electron microscope, myeloperoxidase (MPO) activity by colorimetric method and ICAM-1 protein level detected by western blot, (2) At 3 h after phosgene exposure, protective effects of different dosages of PTX (50 mg/kg and 100 mg/kg) administration were evaluated by MPO activity, ICAM-1 differential expression and WBC count in bronchoalveolar lavage fluid. The results showed that inflammatory cells emerged out of lung blood vessels at 3 h after phosgene exposure. The MPO activity of lung tissue increased significantly from 3 to 48 h after phosgene exposure (P < 0.05) and ICAM-1 expression presented a similar change, especially at 3 h and 24 h (P < 0.05). After pretreatment and treatment with PTX (100 mg/kg), significant protective effects were shown (P < 0.05). These data supported our hypothesis that PTX reduced phosgene-induced lung injury, possibly by inhibiting ICAM-1 differential expression.

  7. Intercellular Adhesion Molecule-1 and Vascular Cell Adhesion Molecule Are Induced by Ionizing Radiation on Lymphatic Endothelium.

    PubMed

    Rodriguez-Ruiz, María E; Garasa, Saray; Rodriguez, Inmaculada; Solorzano, Jose Luis; Barbes, Benigno; Yanguas, Alba; Teijeira, Alvaro; Etxeberria, Iñaki; Aristu, José Javier; Halin, Cornelia; Melero, Ignacio; Rouzaut, Ana

    2017-02-01

    The goal of this study was to assess the effects of ionizing radiation on the expression of the integrin ligands ICAM-1 and VCAM that control leucocyte transit by lymphatic endothelial cells. Confluent monolayers of primary human lymphatic endothelial cells (LEC) were irradiated with single dose of 2, 5, 10 or 20 Gy, with 6 MeV-x-rays using a Linear-Accelerator. ICAM-1 and VCAM expression was determined by flow cytometry. Human tissue specimens received a single dose of 20 Gy with 15 MeV-x-rays. MC38, B16-OVA or B16-VEGF-C tumors grown in C57BL/6 mice were irradiated with single dose of 20Gy using a Linear-Accelerator fitted with a 10mm Radiosurgery collimator. Clinical samples were obtained from patients previous and 4 weeks after complete standard radiotherapy. ICAM-1 and VCAM expression was detected in all tissue specimens by confocal microscopy. To understand the role of TGFβ in this process anti-TGFβ blocking mAb were injected i.p. 30min before radiotherapy. Cell adhesion to irradiated LEC was analyzed in adhesion experiments performed in the presence or in the absence of anti- TGFβ and /or anti-ICAM1 blocking mAb. We demonstrate that lymphatic endothelial cells in tumor samples experience induction of surface ICAM-1 and VCAM when exposed to ionizing radiation in a dose- and time-dependent manner. These effects can be recapitulated in cultured LEC, and are in part mediated by TGFβ. These data are consistent with increases in ICAM-1 and VCAM expression on LYVE-1+ endothelial cells in freshly explanted human tumor tissue and in mouse transplanted tumors after radiotherapy. Finally, ICAM-1 and VCAM expression accounts for enhanced adherence of human T lymphocytes to irradiated LEC. Our results show induction of ICAM-1 and VCAM on LVs in irradiated lesions and offer a starting point for elucidating the biological and therapeutic implications of targeting leukocyte traffic in combination to immunotherapy. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Brucella abortus as a potential vaccine candidate: induction of interleukin-12 secretion and enhanced B7.1 and B7.2 and intercellular adhesion molecule 1 surface expression in elutriated human monocytes stimulated by heat-inactivated B. abortus.

    PubMed

    Zaitseva, M; Golding, H; Manischewitz, J; Webb, D; Golding, B

    1996-08-01

    Development of a vaccine which is capable of generating a strong cellular immune response associated with gamma interferon (IFN-gamma) production and cytotoxic T-cell development requires that the immunogen be capable of inducing the secretion of interleukin-12 (IL-12), which is a pivotal factor for the differentiation of Th1 or Tc1 cells. We have previously shown that the heat-inactivated gram-negative bacterium Brucella abortus can induce IFN-gamma secretion by T cells. In the present study, we demonstrate that B. abortus and lipopolysaccharide (LPS) from B. abortus can induce IL-12 p40 mRNA expression and protein secretion by human elutriated monocytes (99% pure). p40 mRNA was detected within 4 h, and p40 protein could be measured at 24 h. This induction was abrogated by anti-CD14 monoclonal antibody, suggesting that monocytes recognize B. abortus via their receptor for LPS. The biological activity of IL-12 secreted by B. abortus-stimulated monocytes was demonstrated by its ability to upregulate IFN-gamma mRNA expression in T cells separated from monocytes and B. abortus by a transwell membrane. The B. abortus-induced IL-12 also enhanced NK cytolytic activity against K562 target cells. B. abortus was shown to rapidly increase the expression of the costimulatory molecules B7.1 and B7.2 and intercellular adhesion molecule 1 on human monocytes. Together, these data indicate that B. abortus can directly activate human monocytes and provide the cytokine milieu which would direct the immune response towards Th1-Tc1 differentiation.

  9. Brucella abortus as a potential vaccine candidate: induction of interleukin-12 secretion and enhanced B7.1 and B7.2 and intercellular adhesion molecule 1 surface expression in elutriated human monocytes stimulated by heat-inactivated B. abortus.

    PubMed Central

    Zaitseva, M; Golding, H; Manischewitz, J; Webb, D; Golding, B

    1996-01-01

    Development of a vaccine which is capable of generating a strong cellular immune response associated with gamma interferon (IFN-gamma) production and cytotoxic T-cell development requires that the immunogen be capable of inducing the secretion of interleukin-12 (IL-12), which is a pivotal factor for the differentiation of Th1 or Tc1 cells. We have previously shown that the heat-inactivated gram-negative bacterium Brucella abortus can induce IFN-gamma secretion by T cells. In the present study, we demonstrate that B. abortus and lipopolysaccharide (LPS) from B. abortus can induce IL-12 p40 mRNA expression and protein secretion by human elutriated monocytes (99% pure). p40 mRNA was detected within 4 h, and p40 protein could be measured at 24 h. This induction was abrogated by anti-CD14 monoclonal antibody, suggesting that monocytes recognize B. abortus via their receptor for LPS. The biological activity of IL-12 secreted by B. abortus-stimulated monocytes was demonstrated by its ability to upregulate IFN-gamma mRNA expression in T cells separated from monocytes and B. abortus by a transwell membrane. The B. abortus-induced IL-12 also enhanced NK cytolytic activity against K562 target cells. B. abortus was shown to rapidly increase the expression of the costimulatory molecules B7.1 and B7.2 and intercellular adhesion molecule 1 on human monocytes. Together, these data indicate that B. abortus can directly activate human monocytes and provide the cytokine milieu which would direct the immune response towards Th1-Tc1 differentiation. PMID:8757841

  10. Plasma zinc levels inversely correlate with vascular cell adhesion molecule-1 concentration in children with sickle cell disease.

    PubMed Central

    Kuvibidila, Solo R.; Sandoval, Manuel; Lao, Juan; Velez, Maria; Yu, Lolie; Ode, David; Gardner, Renée; Lane, Gerald; Warrier, Raj P.

    2006-01-01

    Zinc deficiency has been implicated in impaired cell-mediated immunity of children with sickle cell disease (SCD). However, its influence on the expression of vascular cell-adhesion molecule-1 (VCAM-1) on endothelial cells, a protein involved in vasoocclusion, has not been previously investigated. We therefore measured (soluble) sVCAM-1 and zinc in 76 SCD children and 96 non-SCD children, mean age 7.73 years and 11.24 years, respectively. Although mean zinc levels of both groups were within the normal range (approximately 14.5 micromol/l), 14.5 % of SCD and 11% of non-SCD children (without inflammation) had levels below normal (10.7 micromol/L). Mean sVCAM-1 concentrations of SCD children (837 microg/l) were significantly higher than those of controls (627 microg/l) (p < 0.001). Differences persisted after taking into account age, hemoglobin phenotype, and inflammation (alpha-l acid glycoprotein >l g/l and C-reactive protein >10 mg/I). sVCAM-1 negatively correlated with serum (r = -0.444) and red blood cells zinc (r = -0.242, p < 0.05) but not with acute-phase proteins. Mean sVCAM-1 tended to be higher in SCD children with than in those without a history of a health problem (infection, pain crisis or were transfused; not significant). Data suggest that zinc may modulate the clinical status of SCD children through VCAM-1 expression, and zinc supplementation may be beneficial in these patients. PMID:16916123

  11. Micromanipulation of adhesion of phorbol 12-myristate-13-acetate-stimulated T lymphocytes to planar membranes containing intercellular adhesion molecule-1.

    PubMed Central

    Tözeren, A; Mackie, L H; Lawrence, M B; Chan, P Y; Dustin, M L; Springer, T A

    1992-01-01

    This paper presents an analytical and experimental methodology to determine the physical strength of cell adhesion to a planar membrane containing one set of adhesion molecules. In particular, the T lymphocyte adhesion due to the interaction of the lymphocyte function associated molecule 1 on the surface of the cell, with its counter-receptor, intercellular adhesion molecule-1 (ICAM-1), on the planar membrane, was investigated. A micromanipulation method and mathematical analysis of cell deformation were used to determine (a) the area of conjugation between the cell and the substrate and (b) the energy that must be supplied to detach a unit area of the cell membrane from its substrate. T lymphocytes stimulated with phorbol 12-myristate-13-acetate (PMA) conjugated strongly with the planar membrane containing purified ICAM-1. The T lymphocytes attached to the planar membrane deviated occasionally from their round configuration by extending pseudopods but without changing the size of the contact area. These adherent cells were dramatically deformed and then detached when pulled away from the planar membrane by a micropipette. Detachment occurred by a gradual decrease in the radius of the contact area. The physical strength of adhesion between a PMA-stimulated T lymphocyte and a planar membrane containing 1,000 ICAM-1 molecules/micron 2 was comparable to the strength of adhesion between a cytotoxic T cell and its target cell. The comparison of the adhesive energy density, measured at constant cell shape, with the model predictions suggests that the physical strength of cell adhesion may increase significantly when the adhesion bonds in the contact area are immobilized by the actin cytoskeleton. Images FIGURE 2 FIGURE 4 FIGURE 5 FIGURE 8 FIGURE 9 PMID:1358239

  12. Dual role of the actin cytoskeleton in regulating cell adhesion mediated by the integrin lymphocyte function-associated molecule-1.

    PubMed Central

    Lub, M; van Kooyk, Y; van Vliet, S J; Figdor, C G

    1997-01-01

    Intracellular signals are required to activate the leukocyte-specific adhesion receptor lymphocyte function-associated molecule-1 (LFA-1; CD11a/CD18) to bind its ligand, intracellular adhesion molecule-1 (ICAM-1). In this study, we investigated the role of the cytoskeleton in LFA-1 activation and demonstrate that filamentous actin (F-actin) can both enhance and inhibit LFA-1-mediated adhesion, depending on the distribution of LFA-1 on the cell surface. We observed that LFA-1 is already clustered on the cell surface of interleukin-2/phytohemagglutinin-activated lymphocytes. These cells bind strongly ICAM-1 and disruption of the actin cytoskeleton inhibits adhesion. In contrast to interleukin-2/phytohemagglutinin-activated peripheral blood lymphocytes, resting lymphocytes, which display a homogenous cell surface distribution of LFA-1, respond poorly to intracellular signals to bind ICAM-1, unless the actin cytoskeleton is disrupted. On resting peripheral blood lymphocytes, uncoupling of LFA-1 from the actin cytoskeleton induces clustering of LFA-1 and this, along with induction of a high-affinity form of LFA-1, via "inside-out" signaling, results in enhanced binding to ICAM-1, which is dependent on intact intermediate filaments, microtubules, and metabolic energy. We hypothesize that linkage of LFA-1 to cytoskeletal elements prevents movement of LFA-1 over the cell surface, thus inhibiting clustering and strong ligand binding. Release from these cytoskeletal elements allows lateral movement and activation of LFA-1, resulting in ligand binding and "outside-in" signaling, that subsequently stimulates actin polymerization and stabilizes cell adhesion. Images PMID:9190212

  13. Regulation of leukocyte-endothelium interaction and leukocyte transendothelial migration by intercellular adhesion molecule 1-fibrinogen recognition.

    PubMed

    Languino, L R; Duperray, A; Joganic, K J; Fornaro, M; Thornton, G B; Altieri, D C

    1995-02-28

    Although primarily recognized for its role in hemostasis, fibrinogen is also required for competent inflammatory reactions in vivo. It is now shown that fibrinogen promotes adhesion to and migration across an endothelial monolayer of terminally differentiated myelomonocytic cells. This process does not require chemotactic/haptotactic gradients or cytokine stimulation of the endothelium and is specific for the association of fibrinogen with intercellular adhesion molecule 1 (ICAM-1) on endothelium. Among other adhesive plasma proteins, fibronectin fails to increase the binding of leukocytes to endothelium, or transendothelial migration, whereas vitronectin promotes the binding but not the migration. The fibrinogen-mediated leukocyte adhesion and transendothelial migration could be inhibited by a peptide from the fibrinogen gamma-chain sequence N117NQKIVNL-KEKVAQLEA133, which blocks the binding of fibrinogen to ICAM-1. This interaction could also be inhibited by new anti-ICAM-1 monoclonal antibodies that did not affect the ICAM-1-CD11a/CD18 recognition, thus suggesting that the fibrinogen binding site on ICAM-1 may be structurally distinct from regions previously implicated in leukocyte-endothelium interaction. Therefore, binding of fibrinogen to vascular cell receptors is sufficient to initiate (i) increased leukocyte adhesion to endothelium and (ii) leukocyte transendothelial migration. These two processes are the earliest events of immune inflammatory responses and may also contribute to atherosclerosis.

  14. Inside-out Signaling Promotes Dynamic Changes in the Carcinoembryonic Antigen-related Cellular Adhesion Molecule 1 (CEACAM1) Oligomeric State to Control Its Cell Adhesion Properties*

    PubMed Central

    Patel, Prerna C.; Lee, Hannah S. W.; Ming, Aaron Y. K.; Rath, Arianna; Deber, Charles M.; Yip, Christopher M.; Rocheleau, Jonathan V.; Gray-Owen, Scott D.

    2013-01-01

    Cell-cell contacts are fundamental to multicellular organisms and are subject to exquisite levels of control. The carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) can engage in both cis-homophilic (parallel) oligomerization and trans-homophilic (anti-parallel) binding. In this study, we establish that the CEACAM1 transmembrane domain has a propensity to form cis-dimers via the transmembrane-embedded 432GXXXG436 motif and that this basal state is overcome when activated calmodulin binds to the CEACAM1 cytoplasmic domain. Although mutation of the 432GXXXG436 motif reduced CEACAM1 oligomerization, it did not affect surface localization of the receptor or influence CEACAM1-dependent cellular invasion by the pathogenic Neisseria. The mutation did, however, have a striking effect on CEACAM1-dependent cellular aggregation, increasing both the kinetics of cell-cell association and the size of cellular aggregates formed. CEACAM1 association with tyrosine kinase c-Src and tyrosine phosphatases SHP-1 and SHP-2 was not affected by the 432GXXXG436 mutation, consistent with their association with the monomeric form of wild type CEACAM1. Collectively, our results establish that a dynamic oligomer-to-monomer shift in surface-expressed CEACAM1 facilitates trans-homophilic binding and downstream effector signaling. PMID:24005674

  15. Kinin B1 receptor regulates interactions between neutrophils and endothelial cells by modulating the levels of Mac-1, LFA-1 and intercellular adhesion molecule-1.

    PubMed

    Figueroa, Carlos D; Matus, Carola E; Pavicic, Francisca; Sarmiento, Jose; Hidalgo, Maria A; Burgos, Rafael A; Gonzalez, Carlos B; Bhoola, Kanti D; Ehrenfeld, Pamela

    2015-04-01

    Kinins are pro-inflammatory peptides that mimic the cardinal features of inflammation. We examined the concept that expression levels of endothelial intercellular adhesion molecule-1 (ICAM-1) and neutrophil integrins Mac-1 and LFA-1 are modulated by the kinin B1 receptor (B1R) agonist, Lys-des[Arg(9)]bradykinin (LDBK). Stimulation of endothelial cells with LDBK increased the levels of ICAM-1 mRNA transcripts/protein, and also of E-selectin and platelet endothelial adhesion molecule-1. ICAM-1 levels increased in a magnitude comparable with that produced by TNF-α. This stimulatory effect was reduced when endothelial cells, which had been previously transfected with a B1R small interfering RNA, were stimulated with LDBK, under comparable conditions. Similarly, LDBK produced a significant increase in protein levels of LFA-1 and Mac-1 integrins in human neutrophils, an effect that was reversed by pretreatment of cells with 10 µg/ml cycloheximide or a B1R antagonist. Functional experiments performed with post-confluent monolayers of endothelial cells stimulated with LDBK and neutrophils primed with TNF-α, and vice versa, resulted in enhanced adhesiveness between both cells. Neutralizing Abs to ICAM-1 and Mac-1 reduced the adhesion between them. Our results indicate that kinin B1R is a novel modulator that promotes adhesion of leukocytes to endothelial cells, critically enhancing the movement of neutrophils from the circulation to sites of inflammation. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  16. Induction of intercellular adhesion molecule-1 (CD54) on human hepatoma cell line HepG2: influence of cytokines and hepatitis B virus-DNA transfection.

    PubMed Central

    Volpes, R; van den Oord, J J; Desmet, V J; Yap, S H

    1992-01-01

    Human hepatocyte expression of intercellular adhesion molecule-1 (ICAM-1) (CD54) was studied in vitro by exposing the well differentiated human hepatoblastoma cell line HepG2 to various cytokines. In addition, hepatitis B virus (HBV)-DNA transfected HepG2 cells were also analysed. Expression of ICAM-1 on HepG2 cells was then revealed with an immunohistochemical procedure. Untreated HepG2 cells were unreactive, but showed strong cytoplasmic ICAM-1 immunoreactivity after treatment with interferon-gamma (IFN-gamma). This induction was completely inhibited by addition of a neutralizing antibody directed to IFN-gamma. IL-1, IL-6, tumour necrosis factor-alpha (TNF-alpha) and IFN-alpha, used alone or in combination, did not induce ICAM-1 expression, neither did they inhibit the IFN-gamma-induced expression of this adhesion molecule on HepG2 cells. Untreated hepatitis B virus-DNA transfected HepG2 cells expressed membranous ICAM-1. These results indicate that IFN-gamma is the main cytokine trigger for ICAM-1 expression on HepG2 cells, suggesting that in areas of liver inflammation this adhesion molecule is up-regulated on hepatocytes by locally released IFN-gamma. In addition, expression of ICAM-1 by hepatitis B virus-DNA transfected HepG2 cells suggests other, still unknown, triggering mechanisms in the induction of such adhesion molecules, for instance gene activation by viral genome, or autocrine virus-induced hepatocellular cytokine production. Images Fig. 1 Fig. 2 PMID:1346374

  17. The relationship between platelet endothelial cell adhesion molecule-1 and paraquat-induced lung injury in rabbits

    PubMed Central

    Shi, Jing; Hu, Chun-lin; Gao, Yu-feng; Liao, Xiao-xing; Xu, Hope

    2012-01-01

    BACKGROUND: Platelet endothelial cell adhesion molecule-1 (PECAM-1), also known as CD31, is mainly distributed in vascular endothelial cells. Studies have shown that PECAM-1 is a very significant indicator of angiogenesis, and has been used as an indicator for vascular endothelial cells. The present study aimed to explore the relationship between the expression of PECAM-1 and the degree of acute lung injury (ALI) and fibrosis in paraquat (PQ) induced lung injury in rabbits. METHODS: Thirty-six adult New Zealand rabbits were randomly divided into three groups (12 rabbits in each group) according to PQ dosage: 8 mg/kg (group A), 16 mg/kg (group B), and 32 mg/kg (group C). After PQ infusion, the rabbits were monitored for 7 days and then euthanized. The lungs were removed for histological evaluation. Masson staining was used to determine the degree of lung fibrosis (LF), and semi-quantitative immune-histochemistry analysis to determine the expression of PECAM-1. Pearson’s product-moment correlation analysis was performed to evaluate the relationship between the expression of PECAM-1 and the extent of lung injuries expressed by ALI score and degree of LF. RESULTS: Rabbits in the three groups showed apparent poisoning. The rabbits survived longer in group A than in groups B and C (6.47±0.99 days vs. 6.09±1.04 days vs. 4.77±2.04 days) (P<0.05). ALI score was lower in group A than in groups B and C (8.33±1.03 vs. 9.83±1.17 vs. 11.50±1.38) (P<0.05), and there was statistically significant difference between group B and group C (P=0.03). LF was slighter in group A than in groups B and C (31.09%±2.05 % vs. 34.37%±1.62 % vs. 36.54%±0.44%) (P<0.05), and there was statistically significant difference between group B and group C (P=0.026). The PEACAM-1 expression was higher in group A than in groups B and C (20.31%±0.70% vs. 19.34%±0.68% vs. 18.37%±0.46%) (P<0.05), and there was statistically significant difference between group B and group C (P=0.017). Pearson

  18. Associations of soluble intercellular adhesion molecule-1 with carotid atherosclerosis progression.

    PubMed

    Kondo, Kimito; Kitagawa, Kazuo; Nagai, Yoji; Yamagami, Hiroshi; Hashimoto, Hiroyuki; Hougaku, Hidetaka; Hori, Masatsugu

    2005-03-01

    Our previous study demonstrated that plasma concentration of high-sensitivity C-reactive protein (hs-CRP) is a marker of carotid atherosclerosis activity. In this study, we investigated whether plasma levels of soluble cell adhesion molecules have potential value to predict atherosclerosis progression. The study included 192 outpatients 40-82 years of age who were treated for traditional risk factor for cardiovascular disease. Patients underwent repeated ultrasonographic evaluation for 53+/-11 months. Severity of atherosclerosis was evaluated by the maximal intimal-medial thickness (max-IMT), plaque number (PN) and plaque score (PS, the sum of all plaque thicknesses). Blood samples were collected for measurement of hs-CRP, soluble intercellular adhesion molecule (sICAM-1) and sP-selectin at the time of baseline examination. The development of atherosclerosis was estimated by the formula: Deltavalue/year=(last value-baseline value)/number of follow-up years. Multivariate linear regression analysis revealed that sICAM-1 was associated with DeltaIMT/year and DeltaPS/year, which was not the case for sP-selectin. sICAM-1 was closely associated with DeltaIMT/year especially in patients with apparent atheromatous plaque. Our results suggested that levels of sICAM-1 might have predictive value of progression of carotid atherosclerosis independently of traditional risk factors and hs-CRP.

  19. The intracellular domain of cell adhesion molecule 1 is present in emphysematous lungs and induces lung epithelial cell apoptosis.

    PubMed

    Hagiyama, Man; Yoneshige, Azusa; Inoue, Takao; Sato, Yasufumi; Mimae, Takahiro; Okada, Morihito; Ito, Akihiko

    2015-08-11

    Pulmonary emphysema is characterized histologically by destruction of alveolar walls and enlargement of air spaces due to lung epithelial cell apoptosis. Cell adhesion molecule 1 (CADM1) is an immunoglobulin superfamily member expressed in lung epithelial cells. CADM1 generates a membrane-associated C-terminal fragment, αCTF, through A disintegrin- and metalloprotease-10-mediated ectodomain shedding, subsequently releasing the intracellular domain (ICD) through γ-secretase-mediated intramembrane shedding of αCTF. αCTF localizes to mitochondria and induces apoptosis in lung epithelial cells. αCTF contributes to the development and progression of emphysema as a consequence of increased CADM1 ectodomain shedding. The purpose of this study was to examine whether the ICD makes a similar contribution. The ICD was synthesized as a 51-amino acid peptide, and its mutant was synthesized by substituting seven amino acids and deleting two amino acids. These peptides were labeled with fluorescein isothiocyanate and were introduced into various cell lines. ICD peptide-derived fluorescence was well visualized in lung epithelial cells at the site of Mitotracker mitochondrial labeling, but was detected in locations other than mitochondria in other cell types. Mutant peptide-derived fluorescence was detected in locations other than mitochondria, even in lung epithelial cells. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assays revealed that transduction of the ICD peptide increased the proportion of apoptotic cells 2- to 5-fold in the lung epithelial cell lines, whereas the mutant peptide did not. Abundance of the ICD was below the Western blot detection limit in emphysematous (n = 4) and control (n = 4) human lungs. However, the ICD was detected only in emphysematous lungs when it was immunoprecipitated with anti-CADM1 antibody (4/4 vs. 0/4, P = 0.029). As the abundance of ICD molecules was sparse but present, increased CADM1 shedding

  20. Hyperhyaluronanemia in alcoholic hepatitis is associated with increased levels of circulating soluble intercellular adhesion molecule-1.

    PubMed

    Hill, D B; Deaciuc, I V; McClain, C J

    1998-09-01

    The purpose of this study was to evaluate the role of the sinusoidal endothelial cell (SEC) during the clinical course of alcoholic hepatitis. Twenty consenting patients (mean age: 49.4 +/- 11.0 years) with moderate or severe hepatitis were studied. The patients were selected and characterized according to their history of drinking and laboratory profile, including serum aminotransferases, bilirubin, total white blood cell and neutrophil count, and prothrombin times. C-reactive protein and interleukin-6 were also measured as markers of the hepatic acute phase response. A marker of the SEC functional state, the circulating level of hyaluronan, was measured in parallel with the circulating levels of soluble intercellular adhesion molecule (sICAM)-1 over a 6-month observation period. All patients were hospitalized for the first month and encouraged to abstain from drinking for the duration of the study. The initial increased levels of both hyaluronan (542 +/- 32 ng x ml(-1) serum) and sICAM-1 (488 +/- 70 ng x ml(-1) serum), gradually fell during the 6-month observation period, eventually reaching values close to those seen in healthy subjects. A positive correlation was obtained between changes in these two markers of SEC function/activation on the one hand, and between these two tests and bilirubin, on the other hand. These data indicate that abnormalities of SEC function/activation, as reflected by serum hyaluronan and siCAM-1, are prominent in alcoholic hepatitis, and these alterations improve within relatively short periods of time after cessation of alcohol consumption.

  1. Suppression of complement regulatory protein C1 inhibitor in vascular endothelial activation by inhibiting vascular cell adhesion molecule-1 action

    SciTech Connect

    Zhang, Haimou; Qin, Gangjian; Liang, Gang; Li, Jinan; Chiu, Isaac; Barrington, Robert A.; Liu, Dongxu . E-mail: dxliu001@yahoo.com

    2007-07-13

    Increased expression of adhesion molecules by activated endothelium is a critical feature of vascular inflammation associated with the several diseases such as endotoxin shock and sepsis/septic shock. Our data demonstrated complement regulatory protein C1 inhibitor (C1INH) prevents endothelial cell injury. We hypothesized that C1INH has the ability of an anti-endothelial activation associated with suppression of expression of adhesion molecule(s). C1INH blocked leukocyte adhesion to endothelial cell monolayer in both static assay and flow conditions. In inflammatory condition, C1INH reduced vascular cell adhesion molecule (VCAM-1) expression associated with its cytoplasmic mRNA destabilization and nuclear transcription level. Studies exploring the underlying mechanism of C1INH-mediated suppression in VCAM-1 expression were related to reduction of NF-{kappa}B activation and nuclear translocation in an I{kappa}B{alpha}-dependent manner. The inhibitory effects were associated with reduction of inhibitor I{kappa}B kinase activity and stabilization of the NF-{kappa}B inhibitor I{kappa}B. These findings indicate a novel role for C1INH in inhibition of vascular endothelial activation. These observations could provide the basis for new therapeutic application of C1INH to target inflammatory processes in different pathologic situations.

  2. Soluble Intracellular Adhesion Molecule-1 in Patients with Unipolar or Bipolar Affective Disorders: Results from a Pilot Trial.

    PubMed

    Schaefer, Martin; Sarkar, Susanne; Schwarz, Markus; Friebe, Astrid

    2016-01-01

    Immunological and vascular markers may play a role in the pathophysiology of mood disorders and mood changes. To test whether the cell adhesion molecule soluble intracellular adhesion molecule-1 (sICAM-1) may serve as a biomarker for patients with unipolar or bipolar affective disorders when compared to a healthy control group, and whether sICAM-1 blood levels change during different mood states. sICAM-1 serum concentrations were compared between 20 healthy controls and 48 patients with affective disorders (unipolar, bipolar II and bipolar I disorder) during different mood states (euthymic mood state, depression or mania). When compared to healthy controls, patients with affective disorders had significantly higher sICAM-1 levels during the euthymic state (p = 0.015). Differences became more pronounced during depression (p = 0.013). When unipolar and bipolar patients were analyzed separately, unipolar patients significantly differed from controls during the euthymic and depressive mood state, while bipolar II patients showed a trend towards higher sICAM-1 levels during depression. Patients with bipolar I disorders had significantly higher sICAM-1 levels during manic states when compared to controls (p = 0.007). sICAM-1 elevation in unipolar and bipolar patients, independent of mood changes, might support the hypothesis of chronic immune activation and endothelial dysfunction in patients with affective disorders. © 2016 S. Karger AG, Basel.

  3. Identification of the binding site in intercellular adhesion molecule 1 for its receptor, leukocyte function-associated antigen 1.

    PubMed Central

    Fisher, K L; Lu, J; Riddle, L; Kim, K J; Presta, L G; Bodary, S C

    1997-01-01

    Intercellular adhesion molecule 1 (ICAM-1, CD54) is a member of the Ig superfamily and is a counterreceptor for the beta 2 integrins: lymphocyte function-associated antigen 1 (LFA-1, CD11a/CD18), complement receptor 1 (MAC-1, CD11b/CD18), and p150,95 (CD11c/CD18). Binding of ICAM-1 to these receptors mediates leukocyte-adhesive functions in immune and inflammatory responses. In this report, we describe a cell-free assay using purified recombinant extracellular domains of LFA-1 and a dimeric immunoadhesin of ICAM-1. The binding of recombinant secreted LFA-1 to ICAM-1 is divalent cation dependent (Mg2+ and Mn2+ promote binding) and sensitive to inhibition by antibodies that block LFA-1-mediated cell adhesion, indicating that its conformation mimics that of LFA-1 on activated lymphocytes. We describe six novel anti-ICAM-1 monoclonal antibodies, two of which are function blocking. Thirty-five point mutants of the ICAM-1 immunoadhesin were generated and residues important for binding of monoclonal antibodies and purified LFA-1 were identified. Nineteen of these mutants bind recombinant LFA-1 equivalently to wild type. Sixteen mutants show a 66-2500-fold decrease in LFA-1 binding yet, with few exceptions, retain binding to the monoclonal antibodies. These mutants, along with modeling studies, define the LFA-1 binding site on ICAM-1 as residues E34, K39, M64, Y66, N68, and Q73, that are predicted to lie on the CDFG beta-sheet of the Ig fold. The mutant G32A also abrogates binding to LFA-1 while retaining binding to all of the antibodies, possibly indicating a direct interaction of this residue with LFA-1. These data have allowed the generation of a highly refined model of the LFA-1 binding site of ICAM-1. Images PMID:9188101

  4. Artemether Combined with shRNA Interference of Vascular Cell Adhesion Molecule-1 Significantly Inhibited the Malignant Biological Behavior of Human Glioma Cells

    PubMed Central

    Wang, Ping; Xue, Yi-Xue; Yao, Yi-Long; Yu, Bo; Liu, Yun-Hui

    2013-01-01

    Artemether is the derivative extracted from Chinese traditional herb and originally used for malaria. Artemether also has potential therapeutic effects against tumors. Vascular cell adhesion molecule-1 (VCAM-1) is an important cell surface adhesion molecule associated with malignancy of gliomas. In this work, we investigated the role and mechanism of artemether combined with shRNA interference of VCAM-1 (shRNA-VCAM-1) on the migration, invasion and apoptosis of glioma cells. U87 human glioma cells were treated with artemether at various concentrations and shRNA interfering technology was employed to silence the expression of VCAM-1. Cell viability, migration, invasiveness and apoptosis were assessed with MTT, wound healing, Transwell and Annexin V-FITC/PI staining. The expression of matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9) and phosphorylated Akt (p-Akt) was checked by Western blot assay. Results showed that artemether and shRNA-VCAM-1 not only significantly inhibited the migration, invasiveness and expression of MMP-2/9 and p-Akt, but also promoted the apoptosis of U87 cells. Combined treatment of both displayed the maximum inhibitory effects on the malignant biological behavior of glioma cells. Our work revealed the potential therapeutic effects of artemether and antiVCAM-1 in the treatments of gliomas. PMID:23593320

  5. Higher serum levels of soluble intracellular cell adhesion molecule-1 and soluble vascular cell adhesion molecule predict peripheral artery disease in haemodialysis patients.

    PubMed

    Cheng, Chi-Hung; Chen, Yi-Shyan; Shu, Kuo-Hsiung; Chang, Horng-Rong; Chou, Ming-Chih

    2012-11-01

    Serum levels of soluble intracellular cell adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM) and monocyte chemotactic protein 1 (MCP-1), are elevated in patients with peripheral artery disease (PAD). However, the levels of these cell adhesion molecules in patients undergoing haemodialysis (HD) are unclear. A total of 112 HD patients were included and PAD was diagnosed using the ankle-brachial index and Doppler ultrasound. Serum levels of sICAM-1, sVCAM-1 and MCP-1 were assayed using enzyme linked immunosorbent assay. Out of 106 HD patients, 31 (27.7%) were diagnosed with PAD. After adjusting for risk factors, higher serum levels of sVCAM-1 and sICAM-1 were associated with PAD in HD patients, with an odds ratio of 5.3 (95% CI 3.3-65.5) and 2.7 (95% CI 1.2-21.8) respectively. Using sVCAM-1 and sICAM-1 for diagnosis of PAD in HD patients, sVCAM-1 had a sensitivity of 72.4% and specificity of 62.3% for sVCAM-1 and sICAM-1 had a sensitivity of 89.3% and a specificity of 40%. MCP-1 was not associated with PAD in HD patients. In addition, the fistula of HD patients with PAD had a lower A-V access flow. sVCAM-1 and sICAM-1 was associated with higher risk of PAD in HD patients. Moreover, HD patients with PAD had a lower blood flow and lower A-V access flow. Our results showed that sVCAM-1 and sICAM-1 may be used as screening markers for PAD in HD patients. © 2012 The Authors. Nephrology © 2012 Asian Pacific Society of Nephrology.

  6. Ligand-induced adhesion to activated endothelium and to vascular cell adhesion molecule-1 in lymphocytes transfected with the N-formyl peptide receptor.

    PubMed

    Honda, S; Campbell, J J; Andrew, D P; Engelhardt, B; Butcher, B A; Warnock, R A; Ye, R D; Butcher, E C

    1994-04-15

    Binding of FMLP to the neutrophil N-formyl peptide receptor (FPR) transmits signals through pertussis toxin-sensitive G proteins triggering Ca2+ flux, superoxide production, granule exocytosis, and neutrophil aggregation and adhesion involving the beta 2 (CD18) integrins. Expression of the FPR in mouse fibroblasts or human kidney cells has been shown to confer an N-formyl peptide-inducible Ca2+ flux in transfectants. Here we demonstrate that the transfected receptor can also support ligand-induced alterations in cellular adhesion. We established stable transfectants of mouse L1-2 pre-B cells with cDNA for human FPR (L1-2 FPR cells). The transfectants bind N-formyl-Nle-Leu-Phe-Nle-Tyr-Lys-fluorescein with 1.4 x 10(5) sites per cell and a dissociation constant of 3.3 nM. Stimulation with FMLP induces a transient Ca2+ flux. FMLP also triggers adhesion of L1-2 FPR cells to TNF-alpha- or LPS-activated bEnd3 cells (mouse brain-derived endothelial cells) and to purified mouse VCAM-1. Binding is inhibited by Abs to VCAM-1 and to the alpha-chain of its lymphocyte receptor (the alpha 4 beta 1 integrin, VLA-4). Stimulation with FMLP does not induce a change in cell surface expression of alpha 4. Induced adhesion to VCAM-1 is rapid, detectable at the earliest times measurable (30 to 60 s after FMLP addition), and is inhibited by pertussis toxin. We conclude that FPR can mediate integrin activation not only in neutrophils but also in lymphocytes, and can trigger rapid adhesion via lymphocyte alpha 4 beta 1. The adhesion of lymphocytes is critical to their migration and targeting; our results suggest the possibility of manipulating adhesive responses through expression of chemoattractant receptors in lymphoid cells engineered for cellular therapy, allowing targeted adhesion and potentially migration in response to locally administered ligands.

  7. Prognostic value of soluble intercellular adhesion molecule-1 (s-ICAM-1) in HIV-infected children.

    PubMed

    Gaddi, E; Laucella, S; Balbaryski, J; Cantisano, C; Barboni, G; Candi, M; Giraudi, V

    2000-12-01

    Central events in the host defence system and immune-mediated damage are tightly regulated by cell adhesion molecules. Sera from 28 human immunodeficiency virus (HIV)-1 infected children divided into groups according to disease severity, six seroreverting (SR) children and 25 healthy controls were studied to detect the presence of soluble intercellular adhesion molecule-1 (s-ICAM-1). Soluble ICAM-1 levels were found to be significantly increased in HIV-infected children in comparison with SR children or healthy controls. Levels of soluble ICAM-1 were higher in patients with severe forms of HIV-infection than in those with a milder form of the disease. Significant differences in titers of s-ICAM-1 were recorded between SR children and HIV-infected children with mild disease or healthy controls. There was a significant correlation between s-ICAM-1 levels and the concentrations of beta 2 microglobulin (beta 2m) and, to a lesser extend, immunoglobulin A levels (IgA). Soluble ICAM-1 levels didn't change considerably in HIV-infected children in stable clinical conditions, independently of their clinical stage of the disease, during a follow-up period of 9-12 months. Conversely, s-ICAM-1 levels increased simultaneously with the appearance of new well-defined clinical disorders or decreased during the improvement of clinical conditions. A significant negative correlation was recorded between the titers of the s-ICAM-1 and the CD4(+) T-cell levels. These results suggest that the s-ICAM-1 might be another useful tool to evaluate disease progression.

  8. Improved monitoring of clinical response in Systemic Lupus Erythematosus by longitudinal trend in soluble vascular cell adhesion molecule-1.

    PubMed

    Lewis, Myles J; Vyse, Simon; Shields, Adrian M; Zou, Lu; Khamashta, Munther; Gordon, Patrick A; Pitzalis, Costantino; Vyse, Timothy J; D'Cruz, David P

    2016-01-08

    To determine whether optimal use of serial measurements of serum levels of soluble cell adhesion molecules (CAM) can improve monitoring of disease activity in SLE. Serum levels of soluble CAM and conventional SLE biomarkers were measured in serial samples (n = 80) from 21 SLE patients during and after flare and correlated in longitudinal analysis with disease activity determined by ECLAM score. Blood samples from a second cohort of 34 SLE patients were subject to flow cytometry to correlate serum biomarkers with B cell subsets. By adjusting for the baseline level (at the first visit), delta soluble vascular cell adhesion molecule-1 (sVCAM-1) showed stronger correlation with changes in ECLAM score and improved sensitivity and specificity for identifying SLE responders versus non-responders compared to conventional SLE biomarkers including anti-dsDNA antibody titre and complement C3. Multiple regression analysis identified delta sVCAM-1 as the best marker of SLE clinical response. sVCAM-1 levels were significantly correlated with CD95(+)CD27(+) activated memory B cells, CD95(+) plasmablasts and circulating plasma cell numbers in SLE patients. Subtracting a baseline level of sVCAM-1 for each individual substantially improved its utility as a biomarker. Delta sVCAM-1 was superior to conventional SLE biomarkers for monitoring changes in disease activity. This suggests that serial monitoring of serum sVCAM-1 trends should be considered in SLE patients to document responses to treatment. We hypothesise that the correlation between activated B cell subsets and circulating plasma cell numbers with soluble VCAM-1 serum levels in SLE may relate to the important role of VCAM-1 in B lymphocyte survival and maturation in bone marrow and secondary lymphoid tissues.

  9. Clinical and prognostic value of combined measurement of cytokines and vascular cell adhesion molecule-1 in premature rupture of membranes.

    PubMed

    Wang, Ying; Wang, Hong-Ling; Chen, Jie; Sun, Jing-Xia

    2016-01-01

    To evaluate whether levels of interleukin 6 (IL-6), interleukin 8 (IL-8), and vascular cell adhesion molecule-1 (VCAM-1) in women with premature rupture of membranes (PROM) differ from those in women without PROM. An observational study of full-term primiparous pregnant women with PROM (PROM group) and those undergoing elective cesarean delivery (control group) was performed at a center in Yangzhou, China, between January 2003 and July 2006. IL-6, IL-8, and VCAM-1 levels were measured in maternal blood, cord blood, and amniotic fluid. A pathologic examination of fetal membranes was conducted. The IL-6, IL-8, and VCAM-1 levels in maternal serum, amniotic fluid, and cord blood were significantly higher in the PROM group (n=58) than in the control group (n=38; P<0.05 for all comparisons). In the PROM group, the levels increased with duration of membrane rupture (P<0.05 for all). Women with chorioamnionitis had significantly higher levels than women without chorioamnionitis (P<0.05 for all), and women with PROM whose newborns had low Apgar score (≤7) had higher levels than those whose newborns had a higher Apgar score (P<0.05 for all). Combined measurements of IL-6, IL-8, and VCAM-1 might help to improve early diagnosis of PROM and chorioamnionitis, and to evaluate the prognosis of newborns. Copyright © 2015 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

  10. Soluble interleukin-2 receptor, intercellular adhesion molecule-1 and interleukin-10 serum levels in patients with melanoma.

    PubMed

    Boyano, M D; Garcia-Vázquez, M D; López-Michelena, T; Gardeazabal, J; Bilbao, J; Cañavate, M L; Galdeano, A G; Izu, R; Díaz-Ramón, L; Raton, J A; Díaz-Pérez, J L

    2000-10-01

    Serum soluble interleukin-2 receptor (sIL-2R), intercellular adhesion molecule-1 (sICAM-1) and interleukin-10 (IL-10) have each been reported as useful markers for melanoma progression. To evaluate the clinical relevance of these three markers, we simultaneously analysed their serum levels in patients with melanoma. A longitudinal study with a 3-year follow-up was performed and different stages of the disease were considered. Mean values of sIL-2R were significantly higher than in normal controls in all stages and correlated with the disease progression. The prognosis of patients with levels > 529 U/ml of sIL-2R was significantly poorer than in patients with sIL-2R levels < 529 U/ml. Levels of sICAM-1 were also elevated in melanoma patients, specially at the time of the metastatic disease. Serum IL-10 levels were more frequently detectable in the patients that developed metastasis during follow-up, and the prognosis of patients with detectable IL-10 levels was significantly poorer than in those patients with IL-10 undetected levels. Statistical analysis based on Logistic and Cox regression models showed that only sex, stage and sIL-2R value are factors significantly associated with metastatic progression. Moreover, high levels of sIL-2R could be a risk factor for malignant progression in melanoma.

  11. Early Detection of Junctional Adhesion Molecule-1 (JAM-1) in the Circulation after Experimental and Clinical Polytrauma.

    PubMed

    Denk, Stephanie; Wiegner, Rebecca; Hönes, Felix M; Messerer, David A C; Radermacher, Peter; Weiss, Manfred; Kalbitz, Miriam; Ehrnthaller, Christian; Braumüller, Sonja; McCook, Oscar; Gebhard, Florian; Weckbach, Sebastian; Huber-Lang, Markus

    2015-01-01

    Severe tissue trauma-induced systemic inflammation is often accompanied by evident or occult blood-organ barrier dysfunctions, frequently leading to multiple organ dysfunction. However, it is unknown whether specific barrier molecules are shed into the circulation early after trauma as potential indicators of an initial barrier dysfunction. The release of the barrier molecule junctional adhesion molecule-1 (JAM-1) was investigated in plasma of C57BL/6 mice 2 h after experimental mono- and polytrauma as well as in polytrauma patients (ISS ≥ 18) during a 10-day period. Correlation analyses were performed to indicate a linkage between JAM-1 plasma concentrations and organ failure. JAM-1 was systemically detected after experimental trauma in mice with blunt chest trauma as a driving force. Accordingly, JAM-1 was reduced in lung tissue after pulmonary contusion and JAM-1 plasma levels significantly correlated with increased protein levels in the bronchoalveolar lavage as a sign for alveolocapillary barrier dysfunction. Furthermore, JAM-1 was markedly released into the plasma of polytrauma patients as early as 4 h after the trauma insult and significantly correlated with severity of disease and organ dysfunction (APACHE II and SOFA score). The data support an early injury- and time-dependent appearance of the barrier molecule JAM-1 in the circulation indicative of a commencing trauma-induced barrier dysfunction.

  12. Circulating thrombomodulin and vascular cell adhesion molecule-1 and renal vascular lesion in patients with lupus nephritis.

    PubMed

    Yao, G H; Liu, Z H; Zhang, X; Zheng, C X; Chen, H P; Zeng, C H; Li, L S

    2008-08-01

    Currently, the detection of renal vascular lesions (VLS) in lupus nephritis (LN) mainly depends on biopsy examination, and lack surrogate biomarkers for clinical dynamic evaluation. The aim of the present study is to explore the correlation between circulatory endothelial damage biomarkers and VLS. Soluble E-selectin, thrombomodulin (TM) and vascular cell adhesion molecule-1 (VCAM-1) were measured by ELISA. TM and VCAM-1 levels both were significantly elevated in LN with VLS than in LN without VLS (P < 0.01). However, the serum E-selectin was not significantly changed in LN patients with and without VLS. A positive correlation was found between TM and serum creatinine (r = 0.617, P < 0.05) in patients with vascular lesions. In order to further analyse the relationship between TM level and severity degree of vascular lesions in LN patients, we subdivided the patients with vascular lesions into two groups: with thrombotic microangiopathy (TMA) and without TMA. TM level of the patients with TMA is significantly higher than those without TMA (P < 0.01). In conclusion, combined with renal pathological examination, monitoring the circulatory levels of TM and VCAM-1, can provide circulating biomarkers of VLS in LN patients.

  13. Hematopoietic Progenitor Cell Rolling in Bone Marrow Microvessels: Parallel Contributions by Endothelial Selectins and Vascular Cell Adhesion Molecule 1

    PubMed Central

    Mazo, Irina B.; Gutierrez-Ramos, Jose-Carlos; Frenette, Paul S.; Hynes, Richard O.; Wagner, Denisa D.; von Andrian, Ulrich H.

    1998-01-01

    We have used intravital microscopy to study physiologically perfused microvessels in murine bone marrow (BM). BM sinusoids and venules, but not adjacent bone vessels, supported rolling interactions of hematopoietic progenitor cells. Rolling did not involve L-selectin, but was partially reduced in wild-type mice treated with antibodies to P- or E-selectin and in mice that were deficient in these two selectins. Selectin-independent rolling was mediated by α4 integrins, which interacted with endothelial vascular cell adhesion molecule (VCAM)-1. Parallel contribution of the endothelial selectins and VCAM-1 is not known to direct blood cell trafficking to other noninflamed tissues. This combination of constitutively expressed adhesion molecules may thus constitute a BM-specific recruitment pathway for progenitor cells analogous to the vascular addressins that direct selective lymphocyte homing to lymphoid organs. PMID:9687524

  14. Human T-cell lymphotropic virus type 1 (HTLV-1)-induced syncytium formation mediated by vascular cell adhesion molecule-1: evidence for involvement of cell adhesion molecules in HTLV-1 biology.

    PubMed Central

    Hildreth, J E; Subramanium, A; Hampton, R A

    1997-01-01

    While studying the potential role of vascular cell adhesion molecule-1 (VCAM-1) in infection of endothelial cells by human immunodeficiency virus (HIV), we found that VCAM-1 can mediate human T-cell lymphotropic virus type 1 (HTLV-1)-induced syncytium formation. Both expression-vector-encoded and endogenously expressed VCAM-1 supported fusion of uninfected cells with HTLV-1-infected cells. Fusion was obtained with cell lines carrying the HTLV-1 genome and expressing viral proteins but not with an HTLV-1-transformed cell line that does not express viral proteins. In clones of VCAM-1-transfected cells, the degree of syncytium formation observed directly reflected the level of VCAM-1 expression. Syncytium formation between HTLV-1-expressing cells and VCAM-1+ cells could be blocked with antiserum against HTLV-1 gp46 and with a monoclonal antibody (MAb) against VCAM-1. Fusion was not blocked by antiserum against HIV or a MAb against VLA-4, the physiological counter-receptor for VCAM-1. The results indicate that VCAM-1 can serve as an accessory molecule or potential coreceptor for HTLV-1-induced cell fusion and provide direct evidence of a role for cell adhesion molecules in the biology of HTLV-1. PMID:8995639

  15. Serum activated leukocyte cell adhesion molecule and intercellular adhesion molecule-1 in patients with gastric cancer: Can they be used as biomarkers?

    PubMed

    Erturk, Kayhan; Tastekin, Didem; Bilgin, Elif; Serilmez, Murat; Bozbey, Hamza Ugur; Sakar, Burak

    2016-02-01

    Cellular adhesion molecules might be used as markers in diagnosis and prognosis in some types of malignant tumors. The purpose of this study was to determine the clinical significance of the serum levels of activated leukocyte cell adhesion molecule-1 (ALCAM) and intercellular adhesion molecule-1 (ICAM-1) in gastric cancer (GC) patients. Fifty-eight GC patients and 20 age- and sex-matched healthy controls were enrolled into this study. Pretreatment serum markers were determined by the solid-phase sandwich enzyme-linked immunosorbent assay (ELISA). The median age at diagnosis was 59.5 years (range 32-82 years). Tumor localizations of the majority of the patients were antrum (n=42, 72.4%) and tumor histopathologies of the majority of the patients were diffuse (n=43, 74.1%). The majority of the patients had stage IV disease (n=41, 70.7%). Thirty six (62.1%) patients had lymph node involvement. The median follow-up time was 66 months (range 1-97.2 months). At the end of the observation period, 26 patients (44.8%) were dead. The median survival for all patients was 21.4±5 months (%95 CI, 11.5-31.3). The 1-year survival rates were 66.2%. The baseline serum ALCAM levels of the patients were significantly higher than those of the controls (p=0.001). There was no significant difference in the serum levels of ICAM-1 between the patients and controls (p=0.232). No significant correlation was detected between the levels of the serum markers and other clinical parameters (p>0.05). Tumor localization (p=0.03), histopathology (p=0.05), and response to chemotherapy (p=0.003) had prognostic factors on survival. Neither serum ALCAM levels nor serum ICAM-1 levels were identified to have a prognostic role on overall survival (ICAM-1 p=0.6, ALCAM p=0.25). In conclusion, serum levels of ALCAM were found to have diagnostic value in GC patients. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  16. Platelet Endothelial Cell Adhesion Molecule-1 Gene Polymorphisms are Associated with Coronary Artery Lesions in the Chronic Stage of Kawasaki Disease.

    PubMed

    Lu, Wen-Hsien; Huang, Sin-Jhih; Yuh, Yeong-Seng; Hsieh, Kai-Sheng; Tang, Chia-Wan; Liou, Huei-Han; Ger, Luo-Ping

    2017-05-01

    Kawasaki disease is the most common cause of pediatric acquired heart disease. The role of platelet endothelial cell adhesion molecule-1 in the inflammatory process has been documented. To date, no report has investigated the relationship between coronary artery lesions of Kawasaki disease and platelet endothelial cell adhesion molecule-1 polymorphisms. A total of 114 Kawasaki disease children with coronary artery lesions and 185 Kawasaki disease children without coronary artery lesions were recruited in this study. The TaqMan assay was conducted to identify the genotype in this case-control study. In three single nucleotide polymorphisms (Leu125Val, Ser563Asn, and Arg670Gly) of platelet endothelial cell adhesion molecule-1, we found that the Leu-Ser-Arg haplotype was associated with a significantly increased risk for coronary artery lesions in the chronic stage (odds ratio 3.05, 95% confidence interval 1.06-8.80, p = 0.039), but not for coronary artery lesions in the acute stage. Analysis based on the diplotypes of platelet endothelial cell adhesion molecule-1 also showed that Kawasaki disease with one or two alleles of Leu-Ser-Arg had a significantly increased risk of chronic coronary artery lesions (odds ratio 3.38, 95% confidence interval 1.11-10.28, p = 0.032) and had increased platelet counts after Kawasaki disease was diagnosed, as compared to those with other diplotypes. The haplotype of platelet endothelial cell adhesion molecule-1 Leu-Ser-Arg might be associated with the increased platelet counts and the following risk of chronic coronary artery lesions in a dominant manner in Kawasaki disease.

  17. Leptin Resistance Contributes to Obesity in Mice with Null Mutation of Carcinoembryonic Antigen-related Cell Adhesion Molecule 1.

    PubMed

    Heinrich, Garrett; Russo, Lucia; Castaneda, Tamara R; Pfeiffer, Verena; Ghadieh, Hilda E; Ghanem, Simona S; Wu, Jieshen; Faulkner, Latrice D; Ergün, Süleyman; McInerney, Marcia F; Hill, Jennifer W; Najjar, Sonia M

    2016-05-20

    Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) promotes hepatic insulin clearance. Consistently, mice with null mutation of Ceacam1 (Cc1(-/-)) exhibit impaired insulin clearance with increased lipid production in liver and redistribution to white adipose tissue, leading to visceral obesity at 2 months of age. When the mutation is propagated on the C57/BL6J genetic background, total fat mass rises significantly with age, and glucose intolerance and systemic insulin resistance develop at 6 months of age. This study was carried out to determine the mechanisms underlying the marked increase in total fat mass in 6-month-old mutants. Indirect calorimetry analysis showed that Cc1(-/-) mice develop hyperphagia and a significant reduction in physical activity, in particular in the early hours of the dark cycle, during which energy expenditure is only slightly lower than in wild-type mice. They also exhibit increased triglyceride accumulation in skeletal muscle, due in part to incomplete fatty acid β-oxidation. Mechanistically, hypothalamic leptin signaling is reduced, as demonstrated by blunted STAT3 phosphorylation in coronal sections in response to an intracerebral ventricular injection of leptin. Hypothalamic fatty-acid synthase activity is also elevated in the mutants. Together, the data show that the increase in total fat mass in Cc1(-/-) mice is mainly attributed to hyperphagia and reduced spontaneous physical activity. Although the contribution of the loss of CEACAM1 from anorexigenic proopiomelanocortin neurons in the arcuate nucleus is unclear, leptin resistance and elevated hypothalamic fatty-acid synthase activity could underlie altered energy balance in these mice. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  18. Maternal soluble vascular cytoplasmic adhesion molecule-1 and fibronectin levels in early- and late-onset preeclamptic pregnancies.

    PubMed

    Dogan, E; Demir, S Cansun; Gulec, U Kucukgoz

    2014-01-01

    The purpose of this study was to investigate maternal plasma soluble vascular cytoplasmic adhesion molecule-1 (sVCAM-1) and fibronectin levels in the patients with early-onset preeclampsia (EOP) and late-onset preeclampsia (LOP) and also to determine whether different mechanisms are involved in these two forms of disorders. The authors performed a case control study consisting of randomly selected 80 healthy pregnant women (group 1 = control group) and 80 preeclamptic women (group 2 = defined study group). Study group consisted of43 patients with EOP and 37 patients with LOP. sVCAM-1 and fibronectin concentrations were measured by enzyme-linked immunosorbent assay (ELISA) and the findings were compared between the groups. The mean levels of sVCAM-1 and fibronectin were significantly higher in the LOP group than those in the normotensive group (p = 0.043 and 0.010 respectively). Markers were significantly different between the two hypertensive groups of pregnancy. The EOP group had a higher level of sVCAM-1 and fibronectin concentration than the LOP group (p = 0.01, for both markers). There was a positive correlation both between the values of plasma fibronectin and the systolic-diastolic blood pressure measurements (r:0.43 and 0.44, respectively), and between sVCAM-1 and the systolic/diastolic blood pressure measurements (r = 0.54 and 0.64, respectively). Increased plasma levels of fibronectin and sVCAM-1 were found in the preeclamptic patients, especially in those with early-onset preeclampsia. These markers might be related to the pathogenesis of different types of preeclampsia.

  19. Plasma soluble vascular adhesion molecule-1 levels are persistently elevated during the first month after colorectal cancer resection.

    PubMed

    Shantha Kumara, H M C; Tohme, Samer T; Herath, Sonali A C; Yan, Xiaohong; Senagore, Anthony J; Nasar, Abu; Kalady, Matthew F; Baxter, Raymond; Whelan, Richard L

    2012-06-01

    Plasma from the second and third weeks after minimally invasive colorectal resection (MICR) has high levels of the proangiogenic proteins VEGF and angiopoietin 2 and also stimulates, in vitro, endothelial cell (EC) proliferation and migration, which are critical to wound and tumor angiogenesis. Soluble vascular cell adhesion molecule-1 (sVCAM-1) stimulates EC chemotaxis and angiogenesis. The impact of MICR on blood levels of sVCAM-1 is unknown. This study's purpose was to determine plasma sVCAM-1 levels after MICR in colorectal cancer (CRC) patients. Blood samples from 90 patients (26% rectal, 74% colon) were obtained preoperatively, on postoperative days (POD) 1 and 3, and at other points during the next 2 months. The late samples were bundled into 7-day time blocks. sVCAM-1 levels were determined in duplicate via ELISA and reported as ng/ml. Student's t test was used for data analysis (significance, P < 0.008 after Bonferroni correction). The mean incision length was 7.3 ± 3.1 cm, and the conversion rate was 3%. Compared with preoperative (PreOp) levels (811.3 ± 233.2), the mean plasma sVCAM-1 level was significantly higher on POD 1 (905.7 ± 292.4, P < 0.001) and POD 3 (977.7 ± 271.8, P < 0.001). Levels remained significantly elevated for the POD 7-13, POD 14-20, POD 21-27, and POD 28-67 time blocks. MICR for CRC is associated with a persistent increase in plasma sVCAM-1 levels during the first month. This sustained increase may promote angiogenesis and stimulate the growth of residual tumor cells early after surgery.

  20. T-lymphocyte responsiveness in murine schistosomiasis mansoni is dependent upon the adhesion molecules intercellular adhesion molecule-1, lymphocyte function-associated antigen-1, and very late antigen-4.

    PubMed Central

    Langley, J G; Boros, D L

    1995-01-01

    Granuloma formation in murine schistosomiasis is dependent on CD4+ Th lymphocytes and requires recruitment and accumulation of inflammatory cells at the site of egg deposition. The present study examined the role of three adhesion molecules, intercellular adhesion molecule-1 (ICAM-1), lymphocyte function-associated antigen-1 (LFA-1), and very late antigen-4 (VLA-4), that participate in cellular recruitment, interaction, and lymphocyte activation during in vitro activation of acutely and chronically infected spleen and liver granuloma lymphocytes. Blockade of ICAM-1, LFA-1, or VLA-4 by rat monoclonal antibody inhibited spleen and granuloma lymphocyte interleukin-2 (IL-2) and IL-4 production as well as lymphoproliferative responses at similar levels (66 to 87%). The down-modulated cytokine and proliferative responses of chronically infected lymphocytes were inhibited to the same extent as their acutely infected counterparts. Cell sorting analysis demonstrated that acutely and chronically infected splenic and granuloma lymphocytes expressed similar levels of LFA-1, ICAM-1, and VLA-4 and that more ICAM-1 was expressed on infected than on uninfected mouse lymphocytes. By exposure of cells to paired monoclonal antibodies at suboptimal doses, it was determined that whereas all three adhesion molecules may participate, only ICAM-1 and LFA-1 showed synergistic interactions in determining lymphocyte responsiveness. These data suggest that spleen and liver granuloma lymphocytes are equally well armed with functional adhesion receptors. Thus, ICAM-1, LFA-1, and VLA-4 play an important accessory role in inflammatory cytokine production and lymphocyte proliferation, and therefore these adhesion molecules may participate in the initiation and maintenance of the granulomatous inflammation. PMID:7558308

  1. Dileucine and PDZ-binding Motifs Mediate Synaptic Adhesion-like Molecule 1 (SALM1) Trafficking in Hippocampal Neurons*

    PubMed Central

    Seabold, Gail K.; Wang, Philip Y.; Petralia, Ronald S.; Chang, Kai; Zhou, Arthur; McDermott, Mark I.; Wang, Ya-Xian; Milgram, Sharon L.; Wenthold, Robert J.

    2012-01-01

    Synaptic adhesion-like molecules (SALMs) are a family of cell adhesion molecules involved in neurite outgrowth and synapse formation. Of the five family members, only SALM1, -2, and -3 contain a cytoplasmic C-terminal PDZ-binding motif. We have found that SALM1 is unique among the SALMs because deletion of its PDZ-binding motif (SALM1ΔPDZ) blocks its surface expression in heterologous cells. When expressed in hippocampal neurons, SALM1ΔPDZ had decreased surface expression in dendrites and the cell soma but not in axons, suggesting that the PDZ-binding domain may influence cellular trafficking of SALMs to specific neuronal locations. Endoglycosidase H digestion assays indicated that SALM1ΔPDZ is retained in the endoplasmic reticulum (ER) in heterologous cells. However, when the entire C-terminal tail of SALM1 was deleted, SALM1 was detected on the cell surface. Using serial deletions, we identified a region of SALM1 that contains a putative dileucine ER retention motif, which is not present in the other SALMs. Mutation of this DXXXLL motif allowed SALM1 to leave the ER and enhanced its surface expression in heterologous cells and neurons. An increase in the number of protrusions at the dendrites and cell body was observed when this SALM1 mutant was expressed in hippocampal neurons. With electron microscopy, these protrusions appeared to be irregular, enlarged spines and filopodia. Thus, enrichment of SALM1 on the cell surface affects dendritic arborization, and intracellular motifs regulate its dendritic versus axonal localization. PMID:22174418

  2. Stress-induced neurogenic inflammation in murine skin skews dendritic cells towards maturation and migration: key role of intercellular adhesion molecule-1/leukocyte function-associated antigen interactions.

    PubMed

    Joachim, Ricarda Alcira; Handjiski, Bori; Blois, Sandra Maria; Hagen, Evelin; Paus, Ralf; Arck, Petra Clara

    2008-11-01

    The skin continuously serves as a biosensor of multiple exogenous stressors and integrates the resulting responses with an individual's central and peripheral endogenous response systems to perceived stress; it also acts to protect against external challenges such as wounding and infection. We have previously shown in mice that stress induces nerve growth factor- and substance P-dependent neurogenic inflammation, which includes the prominent clustering of MHC class II(+) cells. Because the contribution of dendritic cells (DCs) in response to stress is not well understood, we examined the role of DCs in neurogenic inflammation in murine skin using a well-established murine stress model. We show that sound stress increases the number of intradermal langerin(+) and CD11c(+) DCs and induces DC maturation, as indicated by the up-regulated expression of CD11c, MHC class II, and intercellular adhesion molecule-1 (ICAM-1). Blocking of ICAM-1/leukocyte function-associated antigen-1 interactions significantly abrogated the stress-induced numeric increase, maturation, and migration of dermal DCs in vivo and also reduced stress-induced keratinocyte apoptosis and endothelial cell expression of ICAM-1. In conclusion, stress exposure causes a state of immune alertness in the skin. Such adaptation processes may ensure protection from possible infections on wounding by stressors, such as attack by predators. However, present-day stressors have changed and such adaptations appear redundant and may overrun skin homeostasis by inducing immune dermatoses.

  3. Stimulation of the human intercellular adhesion molecule-1 promoter by interleukin-6 and interferon-gamma involves binding of distinct factors to a palindromic response element.

    PubMed

    Caldenhoven, E; Coffer, P; Yuan, J; Van de Stolpe, A; Horn, F; Kruijer, W; Van der Saag, P T

    1994-08-19

    Intercellular adhesion molecule-1 (ICAM-1) is a transmembrane glycoprotein that promotes adhesion in immunological and inflammatory reactions. ICAM-1 is expressed on cells of many lineages and is induced by interleukin-6 (IL-6) and interferon-gamma (IFN-gamma). Functional analysis of ICAM-1 promoter-luciferase constructs in HepG2 cells enabled us to identify a region between -110 and -37 mediating IL-6 and IFN-gamma responsiveness and containing a palindromic IL-6/IFN-gamma response element (pIRE). Site-directed mutagenesis of key nucleotides in the ICAM-1 pIRE abolished the effect of both IL-6 and IFN-gamma stimulation, while this pIRE element was sufficient to confer IL-6 and IFN-gamma responsiveness to a heterologous promoter. We further show by gel retardation analysis that distinct nuclear factors induced by both IL-6 or IFN-gamma specifically bind to this pIRE. Furthermore, treatment with IL-6 results in the formation of multiple complexes while IFN-gamma induces a single binding complex, both in HepG2 and monocytic U937 cells. Differentiation of U937 cells by exposure to 12-O-tetradecanoyl phorbol-13-acetate abolishes response to IL-6 but not IFN-gamma. Supershift data utilizing the ICAM-1 pIRE revealed that IFN-gamma and IL-6 both induce a factor antigenically related to IFN-gamma activation factor. We further provide data suggesting that IL-6 additionally activates an ICAM-1 pIRE binding factor related to the previously described acute-phase response factor in disparate cell types. We therefore conclude that the activation of these related nuclear factors by IL-6 and IFN-gamma is important in the regulation of ICAM-1 gene expression.

  4. Endothelial cells proactively form microvilli-like membrane projections upon intercellular adhesion molecule 1 engagement of leukocyte LFA-1.

    PubMed

    Carman, Christopher V; Jun, Chang-Duk; Salas, Azucena; Springer, Timothy A

    2003-12-01

    Specific leukocyte/endothelial interactions are critical for immunity and inflammation, yet the molecular details of this interaction interface remain poorly understood. Thus, we investigated, with confocal microscopy, the distribution dynamics of the central adhesion molecules ICAM-1 and LFA-1 in this context. Monolayers of activated HUVECs stained with fluorescent anti-ICAM-1 Fabs or Chinese hamster ovary-K1 cells expressing ICAM-1-green fluorescent protein were allowed to bind LFA-1-bearing monocytes, neutrophils, or K562 LFA-1 transfectants. ICAM-1 was rapidly relocalized to newly formed microvilli-like membrane projections in response to binding LFA-1 on leukocytes. These ICAM-1-enriched projections encircled the leukocytes extending up their sides and clustered LFA-1 underneath into linear tracks. Projections formed independently of VCAM-1/very late Ag 4 interactions, shear, and proactive contributions from the LFA-1-bearing cells. In the ICAM-1-bearing endothelial cells, projections were enriched in actin but not microtubules, required intracellular calcium, and intact microfilament and microtubule cytoskeletons and were independent of Rho/Rho kinase signaling. Disruption of these projections with cytochalasin D, colchicine, or BAPTA-AM had no affect on firm adhesion. These data show that in response to LFA-1 engagement the endothelium proactively forms an ICAM-1-enriched cup-like structure that surrounds adherent leukocytes but is not important for firm adhesion. This finding leaves open a possible role in leukocyte transendothelial migration, which would be consistent with the geometry and kinetics of formation of the cup-like structure.

  5. Efficacy of tremacamra, a soluble intercellular adhesion molecule 1, for experimental rhinovirus infection: a randomized clinical trial.

    PubMed

    Turner, R B; Wecker, M T; Pohl, G; Witek, T J; McNally, E; St George, R; Winther, B; Hayden, F G

    1999-05-19

    Attachment of most rhinovirus subtypes to cells depends on a cellular receptor, the intercellular adhesion molecule 1 (ICAM-1). A recombinant soluble ICAM-1 (tremacamra, formerly BIRR 4) has shown possible efficacy in early studies. To determine the efficacy and safety of intranasal administration of tremacamra in experimental rhinovirus colds in humans. Four randomized, double-blind, placebo-controlled trials conducted in January to March 1996. Volunteers between the ages of 18 and 60 years who had an antibody titer of 1:4 or less to the challenge virus. Subjects were isolated in a hotel room during study days 0 to 8; symptoms were recorded through day 14. A total of 198 subjects were randomized, of whom 196 received drug or placebo and were included in the safety analysis. A total of 177 subjects were included in the efficacy analysis. Tremacamra or placebo was given beginning 7 hours before inoculation with rhinovirus type 39 (preinoculation studies) or 12 hours after (postinoculation studies). Tremacamra as an inhaled solution or as a powder (each given preinoculation and postinoculation for a total of 4 studies) and placebo were given in 6 doses at 3-hour intervals daily during days 1 through 7. Recipients of active treatment received 367 microg of tremacamra per nostril per dose for a total of 4.4 mg/d. Effect of tremacamra on infection, as determined by virus isolation and seroconversion, and on illness, as determined by symptom scores, clinical colds, and nasal mucus weights. Treatment-by-study interaction was not significant, so results were pooled for the main analysis. A total of 88 (92%) of the 96 subjects in the placebo groups and 69 (85%) of the 81 subjects in the active treatment groups were infected (P=.19). For placebo vs tremacamra, respectively, the total symptom score (+/- 95% confidence interval [CI]) was 17.6 (+/- 2.7) vs 9.6 (+/- 2.9), the proportion of clinical colds was 64/96 (67% +/- 9%) vs 36/81 (44% +/- 11%), and the nasal mucus weight

  6. Soluble intercellular adhesion molecule-1, D-lactate and diamine oxidase in patients with inflammatory bowel disease

    PubMed Central

    Song, Wei-Bing; Lv, Yong-Hui; Zhang, Zhen-Shu; Li, Ya-Nan; Xiao, Li-Ping; Yu, Xin-Pei; Wang, Yuan-Yuan; Ji, Hong-Li; Ma, Li

    2009-01-01

    AIM: To study the levels of serum soluble intercellular adhesion molecule-1 (sICAM-1), plasma D-lactate and diamine oxidase (DAO) in patients with inflammatory bowel disease (IBD), and the potential clinical significance. METHODS: Sixty-nine patients with IBD and 30 healthy controls were included in this study. The concentration of sICAM-1 was detected with enzyme-linked immunosorbent assay, the level of D-lactate and DAO was measured by spectroscopic analysis, and the number of white blood cells (WBC) was determined by routine procedure. RESULTS: The levels of sICAM-l, DAO, and WBC in IBD patients were significantly higher than those in the control group (P < 0.01). sICAM-l in IBD patients was found to be closely related to the levels of DAO and D-lactate (212.94 ± 69.89 vs 6.35 ± 2.35, P = 0.000), DAO 212.94 ± 69.89 vs 8.65 ± 3.54, P = 0.000) and WBC (212.94 ± 69.89 vs 7.40 ± 2.61, P = 0.000), but no significant difference was observed between patients with ulcerative colitis and patients with Crohn’s disease. The post-treatment levels of sICAM-l, D-lactate and WBC were significantly lower than before treatment (sICAM-l 206.57 ± 79.21 vs 146.21 ± 64.43, P = 0.000), (D-lactate 1.46 ± 0.94 vs 0.52 ± 0.32, P = 0.000) and (WBC 7.24 ± 0.2.33 vs 5.21 ± 3.21, P = 0.000). CONCLUSION: sICAM-1, D-lactate and DAO are closely related to the specific conditions of IBD, and thus could be used as a major diagnostic index. PMID:19701972

  7. Soluble intracellular adhesion molecule-1 secreted by human umbilical cord blood-derived mesenchymal stem cell reduces amyloid-β plaques.

    PubMed

    Kim, J-Y; Kim, D H; Kim, J H; Lee, D; Jeon, H B; Kwon, S-J; Kim, S M; Yoo, Y J; Lee, E H; Choi, S J; Seo, S W; Lee, J I; Na, D L; Yang, Y S; Oh, W; Chang, J W

    2012-04-01

    Presently, co-culture of human umbilical cord blood mesenchymal stem cells (hUCB-MSCs) with BV2 microglia under amyloid-β42 (Aβ42) exposure induced a reduction of Aβ42 in the medium as well as an overexpression of the Aβ-degrading enzyme neprilysin (NEP) in microglia. Cytokine array examinations of co-cultured media revealed elevated release of soluble intracellular adhesion molecule-1 (sICAM-1) from hUCB-MSCs. Administration of human recombinant ICAM-1 in BV2 cells and wild-type mice brains induced NEP expression in time- and dose-dependent manners. In co-culturing with BV2 cells under Aβ42 exposure, knockdown of ICAM-1 expression on hUCB-MSCs by small interfering RNA (siRNA) abolished the induction of NEP in BV2 cells as well as reduction of added Aβ42 in the co-cultured media. By contrast, siRNA-mediated inhibition of the sICAM-1 receptor, lymphocyte function-associated antigen-1 (LFA-1), on BV2 cells reduced NEP expression by ICAM-1 exposure. When hUCB-MSCs were transplanted into the hippocampus of a 10-month-old transgenic mouse model of Alzheimer's disease for 10, 20, or 40 days, NEP expression was increased in the mice brains. Moreover, Aβ42 plaques in the hippocampus and other regions were decreased by active migration of hUCB-MSCs toward Aβ deposits. These data suggest that hUCB-MSC-derived sICAM-1 decreases Aβ plaques by inducing NEP expression in microglia through the sICAM-1/LFA-1 signaling pathway.

  8. Role of nuclear factor-kappa B in the regulation of intercellular adhesion molecule 1 after infection of human bronchial epithelial cells by Bordetella pertussis.

    PubMed

    Ishibashi, Yoshio; Nishikawa, Akemi

    2003-10-01

    Previous work has demonstrated that infection of human bronchial epithelial cells by Bordetella pertussis up-regulates intercellular adhesion molecule-1 (ICAM-1) gene and protein expression. It has also been shown that interaction of the Arg-Gly-Asp (RGD) site of filamentous hemagglutinin (FHA) with host cell very late antigen (VLA)-5 (alpha 5 beta 1 integrin) is required for the up-regulation of epithelial ICAM-1 expression, and that pertussis toxin (PT) impairs this response. We therefore examined the molecular mechanisms leading to B. pertussis-induced ICAM-1 up-regulation in BEAS-2B human bronchial epithelial cells. A colorimetric nuclear factor kappa B (NF-kappa B) activation assay demonstrated that NF-kappa B was activated in response to infection of these cells with B. pertussis. This activation occurred in an FHA(RGD)-dependent manner, and was blocked by an antibody against VLA-5, implying that binding of the RGD to VLA-5 integrin is involved in NF-kappa B activation. Western blot analysis revealed that the activation of NF-kappa B by B. pertussis was preceded by degradation of I kappa B alpha, a major cytoplasmic inhibitor of NF-kappa B. Pretreatment of the BEAS-2B cells with the NF-kappa B inhibitors pyrrolidine dithiocarbamate (PDTC), MG-132, and SN50 resulted in a marked decrease in B. pertussis-induced ICAM-1 expression, implying the involvement of NF-kappa B in ICAM-1 expression. Purified PT abrogated both NF-kappa B activation and I kappa B alpha degradation. These results suggest that ligation of VLA-5 integrin by FHA induces RGD-dependent NF-kappa B activation, thus leading to the up-regulation of epithelial ICAM-1 expression, and that a PT-sensitive G protein may be involved in this signaling pathway.

  9. Intercellular adhesion molecule 1 is a sensitive and diagnostically useful immunohistochemical marker of papillary thyroid cancer (PTC) and of PTC-like nuclear alterations in Hashimoto's thyroiditis

    PubMed Central

    ZHANG, KE; GE, SHU-JIAN; LIN, XIAO-YAN; LV, BEI-BEI; CAO, ZHI-XIN; LI, JIA-MEI; XU, JIA-WEN; WANG, QIANG-XIU

    2016-01-01

    Intercellular adhesion molecule 1 (ICAM-1) is important in the progression of inflammatory responses. Recently, increased levels of ICAM-1 have been reported in a number of types of malignancy. The present study aimed to investigate ICAM-1 expression in papillary thyroid cancer (PTC) and in Hashimoto's thyroiditis (HT) with PTC-like nuclear alterations, and to assess the predictive value of ICAM-1 in thyroid lesions. ICAM-1 expression was retrospectively investigated in 132 consecutive cases of PTC, 72 cases of HT, 10 of follicular cancer, 15 of follicular adenoma, 16 of nodular goiter and 8 samples of normal thyroid tissue using immunohistochemical analyses, and in 42 PTC patients using western blotting. ICAM-1 expression was not detected in normal follicular cells, follicular lesions (adenoma and cancer) and benign nodular hyperplasia, but was frequently overexpressed in PTC cells. ICAM-1 overexpression was associated with extra-thyroidal invasion and lymph node metastasis; no association was found with age, gender, tumor size, multifocality, pathological stage, recurrence or distant metastasis. ICAM-1 expression in HT patients with PTC-like nuclear alterations was significantly higher than that in HT cases with non-PTC-like features. Compared with antibodies against cytokeratin 19, galectin-3 and Hector Battifora mesothelial-1, ICAM-1 was the most sensitive marker for the detection of PTC-like features in HT. These findings demonstrate that ICAM-1 expression is upregulated in PTC and in HT with PTC-like nuclear alterations. This feature may be an important factor in the progression of cancer of the thyroid gland. PMID:26998068

  10. Plasma levels of soluble intercellular adhesion molecule-1 as a biomarker for disease severity of patients with community-acquired pneumonia.

    PubMed

    Chang, Pin-Yu; Tsao, Shih-Ming; Chang, Jer-Hwa; Chien, Ming-Hsien; Hung, Wen-Yueh; Huang, Yi-Wen; Yang, Shun-Fa

    2016-12-01

    Community-acquired pneumonia (CAP) is characterized as an acute inflammation of the lung associated with the activation of macrophages and neutrophils. Intercellular adhesion molecule-1 (ICAM-1) is an essential adhesion molecule involved in immune cell recruitment in lung inflammation. We investigated whether ICAM-1 is a useful biomarker for assessing the disease severity of hospitalized adult patients with CAP. Plasma soluble ICAM-1 (sICAM-1) levels were measured in 78 patients with CAP and 69 healthy controls by using a commercial enzyme-linked immunosorbent assay. The pneumonia severity index scores were used to determine CAP severity in patients upon initial hospitalization. The sICAM-1 and C-reactive protein (CRP) levels decreased significantly in patients with CAP after antibiotic treatment. The plasma concentration of sICAM-1 alone, but not CRP, was correlated with CAP severity according to the pneumonia severity index scores (r=0.431, p<0.001). The sICAM-1 levels in patients with CAP with high mortality risk were significantly higher than those in patients with CAP with medium or low mortality risk. Moreover, the sICAM-1 level showed a significant correlation with the length of hospital stay (r=0.488, p<0.001). Mechanistic investigations found that bacterial lipopolysaccharide induced upregulation of ICAM-1 expression through the c-Jun N-terminal kinase pathway in RAW264.7 macrophages. Plasma sICAM-1 levels may play a role in the diagnosis and clinical assessment of CAP severity. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Regulation of vascular cell adhesion molecule-1 in dental pulp cells by interleukin-1β: the role of prostanoids.

    PubMed

    Chang, Mei-Chi; Lin, Li-Deh; Zwei-Ching Chang, Jenny; Huang, Chiung-Fang; Chuang, Fu-Hsiung; Lee, Jang-Jaer; Jeng, Po-Yuan; Wang, Tong-Mei; Jeng, Jiiang-Huei

    2012-06-01

    Vascular cell adhesion molecule (VCAM-1) plays a critical role in the inflammatory processes by stimulating the recruitment, extravasation, and migration of leukocytes. Its expression and regulation in the dental pulp is not well elucidated. Primary dental pulp cells were exposed to prostaglandin E(2) (PGE(2)), prostaglandin F(2α) (PGF(2α)), or interleukin 1β (IL-1β) with/without aspirin. VCAM-1 messenger RNA expression was analyzed by reverse transcriptase-polymerase chain reaction. Soluble VCAM-1 (sVCAM-1) in the culture medium was determined by enzyme-linked immunosorbent assay, and the number of viable cells was estimated by (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. IL-1β induced VCAM-1 gene expression of pulp cells. IL-1β also stimulated sVCAM-1 production. The IL-1β-induced sVCAM-1 production was not inhibited but rather enhanced by aspirin, a cyclooxygenase (COX) inhibitor. PGE(2) and PGF(2α) decreased the VCAM-1 expression and sVCAM-1 production of pulp cells. U0126 (1,4-diamino-2,3-dicyano-1,4-bis[2-aminophenylthio]butadiene), a mitogen-activated protein kinase kinase (MEK) inhibitor, attenuated IL-1β-induced sVCAM-1 production. However, no marked cytotoxicity was noted in these experimental conditions as analyzed by MTT assay. IL-1β may be involved in the pulpal inflammatory processes via stimulation of VCAM-1 expression and sVCAM-1 production. This event is not mediated by COX activation and prostanoid production but is associated with MEK signaling. PGE(2) and PGF(2α) may potentially regulate inflammatory processes by the inhibition of VCAM-1. Copyright © 2012 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  12. Effect of Hyperketonemia (Acetoacetate) on Nuclear Factor-κB and p38 Mitogen-Activated Protein Kinase Activation Mediated Intercellular Adhesion Molecule 1 Upregulation in Endothelial Cells

    PubMed Central

    Rains, Justin L.

    2015-01-01

    Abstract Background: Hyperketonemia is a pathological condition observed in patients with type 1 diabetes and ketosis-prone diabetes (KPD), which results in increased blood levels of acetoacetate (AA) and β-hydroxybutyrate (BHB). Frequent episodes of hyperketonemia are associated with a higher incidence of vascular disease. We examined the hypothesis that hyperketonemia activates the nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways that regulate intercellular adhesion molecule 1 (ICAM-1) expression in endothelial cells. Methods: Human umbilical vein endothelial cells (HUVECs) were cultured with AA (0–8 mM) or BHB (0–10 mM) for 0–24 hr. Western blotting was used to determine NF-κB activation in whole-cell lysates. ICAM-1 expression was measured using flow cytometry. Results: Results show a 2.4-fold increase in NF-κB activation in cells treated with 8 mM AA compared to the control. BHB had little or no effect on NF-κB activation. Pretreatment with a reactive oxygen species (ROS) inhibitor [N-acetyl-l-cysteine (NAC)] reduced NF-κB to near-control levels. The expression of AA-induced ICAM-1 was significantly reduced when cells were pretreated with either NAC or p38 MAPK inhibitor. Conclusions: These results suggest that NF-κB and p38 MAPK mediate upregulation of ICAM-1 expression in endothelial cells exposed to elevated levels of AA, which may contribute to the development of vascular disease in diabetes. PMID:25489974

  13. Anionic peptide factor/phosphatidylcholine particles promote the inhibition of vascular cell adhesion molecule-1 in human umbilical vein endothelial cells.

    PubMed

    Lombard, Elise; Marin, Valérie; Domingo, Nicole; Grès, Sandra; Lorec, Anne-Marie; Saunier, Vincent; Arlotto, Emmanuelle; Portugal, Henri; Lairon, Denis; Farnarier, Catherine; Chanussot, Françoise

    2005-01-01

    High-density lipoproteins (HDLs) have significant cardiovascular benefits by retarding the progression of atherosclerosis. One of the mechanisms is the inhibition by HDLs of the vascular cell adhesion molecule-1 (VCAM-1) expression in endothelial cells. Our objective was to test the effect on VCAM-1 expression by the human umbilical vein endothelial cells (HUVEC) of a minor HDL2 and HDL3 apolipoprotein, the anionic peptide factor (APF). The peptide has previously been found to develop some beneficial effects against atherosclerosis, i.e. by promoting the cholesterol efflux from endothelial cells. We examined the effects of two HDL apolipoproteins A-I and APF, either in presence or absence of phosphatidylcholines (PCs), or free PCs, on the expression of VCAM-1 by HUVEC. The cells were stimulated with either the tumor necrosis factor-alpha (TNFalpha, 500 pg/ml) or the calcium bound to heparin (10 microg Ca2+/ml, 50 microg heparin/ml). In the presence of TNFalpha, only the free PCs (0.25 and 1 mM) developed an inhibitory effect (up to 50%). In the absence of TNFalpha and in the presence of calcium bound to heparin, either the lipid-free APF (3.5 microM) or the APF/PC complexes (1:57 molar ratio) or the free PCs (0.25 mM) exhibited a substantial inhibitory effect (72, 71 and 42%, respectively). Our present findings suggest for the first time that one of the mechanisms of the antiatherogenic action of APF involves the inhibition of VCAM-1 expression by HUVEC. The peptide, through its phospholipid-binding and its calcium antagonist abilities, appears to confer on the HDLs a protective effect against the early cellular event of the inflammatory process. Copyright (c) 2005 S. Karger AG, Basel.

  14. Intercellular adhesion molecule-1 (ICAM-1) in Graves' disease: contrast between in vivo and in vitro results.

    PubMed Central

    Ciampolillo, A; Napolitano, G; Mirakian, R; Miyasaki, A; Giorgino, R; Bottazzo, G F

    1993-01-01

    We have reassessed the possible role of the adhesion molecule ICAM-1 in the pathogenesis of thyroid autoimmunity. In order to do that, we have investigated its expression in eight Graves' thyroids both in vivo (i.e. on cryostat sections and on cell suspensions), and in vitro (i.e. on cells cultured in monolayers for 3 days), and the results were compared with those obtained with similar preparations from four normal glands. On cryostat sections, the expression of ICAM-1, and for comparison that of HLA Class I and Class II molecules, was studied by immunofluorescence (IFL), but the former were also assessed by a distinct immunohistochemical technique. ICAM-1 was not detected in thyrocytes in vivo of both normal and Graves' glands, but solely in endothelial cells and antigen-presenting cells (APC). This selective reaction was confirmed by a four-layer technique using specific markers which identify endothelial cells and thyrocytes. HLA Class II molecules were confirmed to be inappropriately expressed in thyrocytes of Graves' glands, but there was no co-expression of these products and ICAM-1 in the same cells. In contrast, ICAM-1 appeared de novo in a proportion of Graves' and normal thyrocytes soon after the attachment and spreading of these cells in monolayer cultures (36-48 h). Graves' thyrocytes showed a quantitatively higher degree of expression compared with that detected on normal thyroid cells (40-70% versus 12-20%). Under these experimental conditions, the four-layer staining with thyroid microsomal antibodies confirmed that thyrocytes were indeed the positive cells which expressed ICAM-1. Blocking experiments with cultured thyrocytes from two Graves' glands and MoAbs to tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) did not prevent the occurrence of ICAM-1 expression. As a result of our study, we failed to demonstrate that Graves' thyrocytes express ICAM-1 in vivo. The unexpected case of inducing ICAM-1 on thyroid cells under

  15. Interleukin-8 and Intercellular Adhesion Molecule 1 Regulation in Oral Epithelial Cells by Selected Periodontal Bacteria: Multiple Effects of Porphyromonas gingivalis via Antagonistic Mechanisms

    PubMed Central

    Huang, George T.-J.; Kim, Daniel; Lee, Jonathan K.-H.; Kuramitsu, Howard K.; Haake, Susan Kinder

    2001-01-01

    Interaction of bacteria with mucosal surfaces can modulate the production of proinflammatory cytokines and adhesion molecules produced by epithelial cells. Previously, we showed that expression of interleukin-8 (IL-8) and intercellular adhesion molecule 1 (ICAM-1) by gingival epithelial cells increases following interaction with several putative periodontal pathogens. In contrast, expression of IL-8 and ICAM-1 is reduced after Porphyromonas gingivalis ATCC 33277 challenge. In the present study, we investigated the mechanisms that govern the regulation of these two molecules in bacterially infected gingival epithelial cells. Experimental approaches included bacterial stimulation of gingival epithelial cells by either a brief challenge (1.5 to 2 h) or a continuous coculture throughout the incubation period. The kinetics of IL-8 and ICAM-1 expression following brief challenge were such that (i) secretion of IL-8 by gingival epithelial cells reached its peak 2 h following Fusobacterium nucleatum infection whereas it rapidly decreased within 2 h after P. gingivalis infection and remained decreased up to 30 h and (ii) IL-8 and ICAM-1 mRNA levels were up-regulated rapidly 2 to 4 h postinfection and then decreased to basal levels 8 to 20 h after infection with either Actinobacillus actinomycetemcomitans, F. nucleatum, or P. gingivalis. Attenuation of IL-8 secretion was facilitated by adherent P. gingivalis strains. The IL-8 secreted from epithelial cells after F. nucleatum stimulation could be down-regulated by subsequent infection with P. gingivalis or its culture supernatant. Although these results suggested that IL-8 attenuation at the protein level might be associated with P. gingivalis proteases, the Arg- and Lys-gingipain proteases did not appear to be solely responsible for IL-8 attenuation. In addition, while P. gingivalis up-regulated IL-8 mRNA expression, this effect was overridden when the bacteria were continuously cocultured with the epithelial cells. The IL-8

  16. A novel anticancer effect of thalidomide: inhibition of intercellular adhesion molecule-1-mediated cell invasion and metastasis through suppression of nuclear factor-kappaB.

    PubMed

    Lin, Yi-Chu; Shun, Chia-Tung; Wu, Ming-Shiang; Chen, Ching-Chow

    2006-12-01

    Thalidomide has been reported to have antiangiogenic and antimetastatic effects. Intercellular adhesion molecule-1 (ICAM-1) was shown to be involved in monocyte adherence to epithelial cells and cancer cell invasion. In this study, we further investigated the role of ICAM-1 in tumorigenesis, including tumor formation and metastasis. ICAM-1 as a molecular target for cancer and the anticancer effect of thalidomide were investigated. Expression of ICAM-1 protein in human lung cancer specimens was assessed by immunohistochemistry. ICAM-1 overexpressing A549 cells (A549/ICAM-1) were established to investigate the direct effect of ICAM-1 on in vitro cell invasion and in vivo tumor metastasis. Transient transfection and luciferase assay, electrophoretic mobility shift assay, and chromatin immunoprecipitation were done to assess the activity and binding of nuclear factor-kappaB to the ICAM-1 promoter. A xenograft model in nude mice was conducted to evaluate the anticancer effect of thalidomide. High expression of ICAM-1 in human lung cancer specimens was correlated with a greater risk of advanced cancers (stages III and IV). A549/ICAM-1 cells were shown to induce in vitro cell invasion and in vivo tumor metastasis. Anti-ICAM-1 antibody and thalidomide had inhibitory effect on these events. Thalidomide also suppressed tumor necrosis factor-alpha-induced ICAM-1 expression through inhibition of nuclear factor-kappaB binding to the ICAM-1 promoter. The in vivo xenograft model showed the effectiveness of thalidomide on tumor formation. These studies provide a framework for targeting ICAM-1 as a biologically based therapy for cancer, and thalidomide might be effective in human lung cancer.

  17. Keishibukuryogan (Gui-Zhi-Fu-Ling-Wan), a Kampo Formula, Decreases Disease Activity and Soluble Vascular Adhesion Molecule-1 in Patients with Rheumatoid Arthritis

    PubMed Central

    Nozaki, Kazuya; Hikiami, Hiroaki; Goto, Hirozo; Nakagawa, Takako; Shibahara, Naotoshi; Shimada, Yutaka

    2006-01-01

    An increasing death rate due to cardiovascular disease in patients with rheumatoid arthritis (RA) has been reported. Keishibukuryogan (KBG) is a traditional Chinese/Japanese (Kampo) formula that has been administered to patients with blood stagnation, e.g. thrombotic disease and atherosclerosis. The objective of this study was to evaluate the efficacy of KBG on disease activity and endothelial dysfunction in RA patients. Sixteen RA patients were enrolled and administered KBG (12 g per day) for 12 weeks in addition to continuing other drugs. The disease activity of RA was assessed by modified disease activity scores for 28 joints (DAS28). Plasma levels of adhesion molecules, soluble E-selectin (sE-selectin), soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) were evaluated. C-reactive protein (CRP), inflammatory cytokines (IL-1β, IL-6 and TNF-α) and lipid peroxide (LPO) were also evaluated. Fourteen patients completed the study. The disease activity of RA, tender joint count, swollen joint count and DAS28 decreased significantly. Among adhesion molecules, only sVCAM-1 decreased significantly. LPO also decreased significantly, whereas CRP and inflammatory cytokines remained unchanged. These results suggest that KBG has insufficient anti-inflammatory or immunomodulating effect but does have a beneficial effect on articular symptoms and a protective effect against endothelial dysfunction in RA patients. PMID:16951720

  18. Interaction between Endothelial Protein C Receptor and Intercellular Adhesion Molecule 1 to Mediate Binding of Plasmodium falciparum-Infected Erythrocytes to Endothelial Cells

    PubMed Central

    Avril, Marion; Bernabeu, Maria; Benjamin, Maxwell; Brazier, Andrew Jay

    2016-01-01

    ABSTRACT Intercellular adhesion molecule 1 (ICAM-1) and the endothelial protein C receptor (EPCR) are candidate receptors for the deadly complication cerebral malaria. However, it remains unclear if Plasmodium falciparum parasites with dual binding specificity are involved in cytoadhesion or different parasite subpopulations bind in brain microvessels. Here, we investigated this issue by studying different subtypes of ICAM-1-binding parasite lines. We show that two parasite lines expressing domain cassette 13 (DC13) of the P. falciparum erythrocyte membrane protein 1 (PfEMP1) family have dual binding specificity for EPCR and ICAM-1 and further mapped ICAM-1 binding to the first DBLβ domain following the PfEMP1 head structure in both proteins. As PfEMP1 head structures have diverged between group A (EPCR binders) and groups B and C (CD36 binders), we also investigated how ICAM-1-binding parasites with different coreceptor binding traits influence P. falciparum-infected erythrocyte binding to endothelial cells. Whereas levels of binding to tumor necrosis factor alpha (TNF-α)-stimulated endothelial cells from the lung and brain by all ICAM-1-binding parasite lines increased, group A (EPCR and ICAM-1) was less dependent than group B (CD36 and ICAM-1) on ICAM-1 upregulation. Furthermore, both group A DC13 parasite lines had higher binding levels to brain endothelial cells (a microvascular niche with limited CD36 expression). This study shows that ICAM-1 is a coreceptor for a subset of EPCR-binding parasites and provides the first evidence of how EPCR and ICAM-1 interact to mediate parasite binding to both resting and TNF-α-activated primary brain and lung endothelial cells. PMID:27406562

  19. Vascular and extravascular immunoreactivity for Intercellular Adhesion Molecule 1 in the orbitofrontal cortex of subjects with major depression: age-dependent changes

    PubMed Central

    Miguel-Hidalgo, Jose Javier; Overholser, James C.; Jurjus, George J.; Meltzer, Herbert Y.; Dieter, Lesa; Konick, Lisa; Stockmeier, Craig A.; Rajkowska, Grazyna

    2011-01-01

    Background Vascular and immune alterations in the prefrontal cortex may contribute to major depression in elderly subjects. Intercellular adhesion molecule-1 (ICAM-1), major inflammatory mediator in vessels and astrocytes, could be altered in geriatric depression, but little is known about its age-dependent expression in subjects with depression and its relationship to astrocytes identified by the marker glial fibrillary acidic protein (GFAP), found to be reduced in depression. Methods We measured the percentage of gray matter area fraction covered by ICAM-1 immunoreactivity in blood vessels and in extravascular accumulations of ICAM-1 immunoreactivity in 19 non-psychiatric comparison subjects and 18 subjects with major depression, all characterized by postmortem psychological diagnosis. Association of extravascular ICAM-1 to GFAP-positive astrocytes was investigated by double-labeling immunofluorescence. Results Vascular and extravascular fractions of ICAM-1 immunoreactivity were lower in subjects with MDD than in non-psychiatric comparison subjects. Non-psychiatric comparison subjects older than 60 experienced dramatic increase in extravascular ICAM-1 immunoreactivity, but this increase was attenuated in elderly subjects with MDD, particularly in those dying by suicide. Most extracellular ICAM-1 immunoreactivity was coextensive with GFAP-immunoreactive astrocytes in both groups. Limitations Heterogeneity in type and dosage of antidepressant medication. Difficulty in determining the exact onset of depression in subjects older than 60 at the time of death. Routine cerebrovascular pathological screening may miss subtle subcellular and molecular changes. Conclusions There is significant attenuation of extravascular and vascular ICAM-1 immunoreactivity in elderly subjects with major depression suggesting an astrocyte-associated alteration in immune function in the aging orbitofrontal cortex of subjects with MDD. PMID:21536333

  20. The Effect of Vitamin D Administration on Intracellular Adhesion Molecule-1 and Vascular Cell Adhesion Molecule-1 Levels in Hemodialysis Patients: A Placebo-controlled, Double-blinded Clinical Trial

    PubMed Central

    Naeini, Afsoon Emami; Moeinzadeh, Firouzeh; Vahdat, Sahar; Ahmadi, Akbar; Hedayati, Zahra Parin; Shahzeidi, Safoora

    2017-01-01

    Objective: Vitamin D deficiency is quite common among end-stage renal disease (ESRD) patients, and Vitamin D administration could reduce morbidity and mortality in these patients through different mechanisms. Cardiovascular diseases are the most common cause of mortality in these patients that are caused by vascular injuries. Intracellular adhesion molecule (ICAM) and vascular cell adhesion molecule (VCAM) are vascular inflammation indicators. The goal of this study is to find the effect of Vitamin D administration on ICAM-1 and VCAM-1 serum levels in ESRD patients on hemodialysis. Methods: The current study is a double-blind, randomized, placebo-controlled clinical trial on 64 patients in two groups of control and treatment. Serum levels of Vitamin D, ICAM-1, and VCAM-1 were measured before and after the study. Treatment group was treated with Vitamin D pearls while control group underwent treatment with placebo pearls. Average serum levels of Vitamin D, ICAM, and VCAM were measured in both groups before and after the study and were analyzed by ANOVA, paired t-test, and Chi-square test using SPSS software. Findings: Sixty-four ESRD patients were recruited for this study consisting of 32 male and 32 female subjects within the ages of 18 and 76 years. The change in serum level of Vitamin D was significant in treatment group (P = 0.001) but not in control group (P > 0.05). Serum levels of ICAM and VCAM also changed significantly in treatment group (P = 0.001) but not in control group (P > 0.05) Conclusion: Based on the findings of this study, it could be said that Vitamin D administration in ESRD patients may increase serum level of Vitamin D up to four times. It also reduces serum levels of ICAM and VCAM which might improve the vascular condition of these patients.

  1. Tumor necrosis factor-alpha enhances neutrophil adhesiveness: induction of vascular cell adhesion molecule-1 via activation of Akt and CaM kinase II and modifications of histone acetyltransferase and histone deacetylase 4 in human tracheal smooth muscle cells.

    PubMed

    Lee, Chiang-Wen; Lin, Chih-Chung; Luo, Shue-Fen; Lee, Hui-Chun; Lee, I-Ta; Aird, William C; Hwang, Tsong-Long; Yang, Chuen-Mao

    2008-05-01

    Up-regulation of vascular cell adhesion molecule-1 (VCAM-1) involves adhesions between both circulating and resident leukocytes and the human tracheal smooth muscle cells (HTSMCs) during airway inflammatory reaction. We have demonstrated previously that tumor necrosis factor (TNF)-alpha-induced VCAM-1 expression is regulated by mitogen-activated protein kinases, nuclear factor-kappaB, and p300 activation in HTSMCs. In addition to this pathway, phosphorylation of Akt and CaM kinase II has been implicated in histone acetyltransferase and histone deacetylase 4 (HDAC4) activation. Here, we investigated whether these different mechanisms participated in TNF-alpha-induced VCAM-1 expression and enhanced neutrophil adhesion. TNF-alpha significantly increased HTSMC-neutrophil adhesions, and this effect was associated with increased expression of VCAM-1 on the HTSMCs and was blocked by the selective inhibitors of Src [4-amino-5-(4-methylphenyl)-7-(t-butyl)pyrazolo[3,4-d]-pyrimidine (PP1)], epidermal growth factor receptor [EGFR; 4-(3'-chloroanilino)-6,7-dimethoxy-quinazoline, (AG1478)], phosphatidylinositol 3-kinase (PI3K) [2-(4-morpholinyl)-8-phenyl-1(4H)-benzopyran-4-one hydrochloride(LY294002) and wortmannin],calcium[1,2-bis(2-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester; BAPTA-AM], phosphatidylinositol-phospholipase C (PLC) [1-[6-[[17beta-methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1H-pyrrole-2,5-dione (U73122)], protein kinase C (PKC) [12-(2-cyanoethyl)-6,7,12, 13-tetrahydro-13-methyl-5-oxo-5H-indolo(2,3-a)pyrrolo(3,4-c)-carbazole (Gö6976), rottlerin, and 3-1-[3-(amidinothio)propyl-1H-indol-3-yl]-3-(1-methyl-1H-indol-3-yl) maleimide (bisindolylmaleimide IX) (Ro 31-8220)], CaM (calmidazolium chloride), CaM kinase II [(8R(*),9S(*),11S(*))-(-)-9-hydroxy-9-methoxycarbonyl-8-methyl-14-n-propoxy-2,3,9, 10-tetrahydro-8,11-epoxy, 1H,8H, 11H-2,7b,11a-triazadibenzo[a,g]cycloocta[cde]trinden-1-one (KT5926) and 1-[N,O-bis(5-isoquinolinesulfonyl

  2. Short-term high-fat diet alters postprandial glucose metabolism and circulating vascular cell adhesion molecule-1 in healthy males.

    PubMed

    Numao, Shigeharu; Kawano, Hiroshi; Endo, Naoya; Yamada, Yuka; Takahashi, Masaki; Konishi, Masayuki; Sakamoto, Shizuo

    2016-08-01

    Short-term intake of a high-fat diet aggravates postprandial glucose metabolism; however, the dose-response relationship has not been investigated. We hypothesized that short-term intake of a eucaloric low-carbohydrate/high-fat diet (LCHF) would aggravate postprandial glucose metabolism and circulating adhesion molecules in healthy males. Seven healthy young males (mean ± SE; age: 26 ± 1 years) consumed either a eucaloric control diet (C, approximately 25% fats), a eucaloric intermediate-carbohydrate/intermediate-fat diet (ICIF, approximately 50% fats), or an LCHF (approximately 70% fats) for 3 days. An oral meal tolerance test (MTT) was performed after the 3-day dietary intervention. The concentrations of plasma glucose, insulin, glucagon-like peptide-1 (GLP-1), intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 (VCAM-1) were determined at rest and during MTT. The incremental area under the curve (iAUC) of plasma glucose concentration during MTT was significantly higher in LCHF than in C (P = 0.009). The first-phase insulin secretion indexes were significantly lower in LCHF than in C (P = 0.04). Moreover, the iAUC of GLP-1 and VCAM-1 concentrations was significantly higher in LCHF than in C (P = 0.014 and P = 0.04, respectively). The metabolites from ICIF and C were not significantly different. In conclusion, short-term intake of eucaloric diet containing a high percentage of fats in healthy males excessively increased postprandial glucose and VCAM-1 concentrations and attenuated first-phase insulin release.

  3. The second domain of intercellular adhesion molecule-1 (ICAM-1) maintains the structural integrity of the leucocyte function-associated antigen-1 (LFA-1) ligand-binding site in the first domain.

    PubMed Central

    Stanley, P; McDowall, A; Bates, P A; Brashaw, J; Hogg, N

    2000-01-01

    The first domain of intercellular adhesion molecule-1 (ICAM-1) binds to the leucocyte function-associated antigen-1 (LFA-1) I domain, which contains the principal ligand-binding site of this leucocyte integrin. Whether the function of the second domain is also to directly bind LFA-1 has been unclear. Our data show that mutation in the hydrophilic EF loop of ICAM-1 domain 2 resulted in impaired binding of the isolated I domain when compared with wild-type ICAM-1. LFA-1 on T-cells also binds with reduced affinity to this ICAM-1 mutant. A hybrid construct containing the first domain of vascular cell-adhesion molecule-1 joined to domains 2-5 of ICAM-1 was unable to bind to the I domain, showing that there is no direct interaction between the second domain of ICAM-1 and the I domain. This construct was also not bound by LFA-1 expressed in T-cells. Function-blocking monoclonal antibodies that map to domain 2 of ICAM-1, implicating this domain in ligand binding, were found to act indirectly. In summary our data suggest that the second domain of ICAM-1 has a role in maintaining the structure of the LFA-1 ligand-binding site in the first domain of ICAM-1 but does not appear to have a direct role in ligand binding. PMID:10998349

  4. Soluble intercellular adhesion molecule-1 (sICAM-1) as a marker of disease relapse in idiopathic uveoretinitis.

    PubMed Central

    Zaman, A G; Edelsten, C; Stanford, M R; Graham, E M; Ellis, B A; Direskeneli, H; D'Cruz, D P; Hughes, G R; Dumonde, D C; Wallace, G R

    1994-01-01

    This study reports the results of a point prevalence study of markers of endothelial dysfunction in the serum of patients with idiopathic uveoretinitis. sICAM-1, soluble endothelial leucocyte adhesion molecule (sELAM), anti-endothelial cell antibodies (AECA) and von Willebrand factor (vWF) levels were measured in 32 patients with isolated idiopathic uveoretinitis and seven with uveitis in association with systemic disease, using commercial and in-house ELISAs. Raised levels of AECA were found in 31% of patients with isolated uveitis, vWF in 28%, sELAM in 15.6% and sICAM-1 in 31%. Further analysis revealed that raised sICAM-1 levels were closely associated with recent relapse of disease (P = 0.00003). Patients with accompanying systemic disease were found to have a similar prevalence of these serum abnormalities to those with isolated ocular disease. In conclusion, vascular endothelial dysfunction may contribute to pathogenesis in uveoretinitis, and in particular sICAM-1 may prove a marker of disease relapse in this condition. PMID:7507016

  5. Amino Acid Sequences Mediating Vascular Cell Adhesion Molecule 1 Binding to Integrin Alpha 4: Homologous DSP Sequence Found for JC Polyoma VP1 Coat Protein

    PubMed Central

    Meyer, Michael Andrew

    2013-01-01

    The JC polyoma viral coat protein VP1 was analyzed for amino acid sequences homologies to the IDSP sequence which mediates binding of VLA-4 (integrin alpha 4) to vascular cell adhesion molecule 1. Although the full sequence was not found, a DSP sequence was located near the critical arginine residue linked to infectivity of the virus and binding to sialic acid containing molecules such as integrins (3). For the JC polyoma virus, a DSP sequence was found at residues 70, 71 and 72 with homology also noted for the mouse polyoma virus and SV40 virus. Three dimensional modeling of the VP1 molecule suggests that the DSP loop has an accessible site for interaction from the external side of the assembled viral capsid pentamer. PMID:24147211

  6. Amino Acid Sequences Mediating Vascular Cell Adhesion Molecule 1 Binding to Integrin Alpha 4: Homologous DSP Sequence Found for JC Polyoma VP1 Coat Protein.

    PubMed

    Meyer, Michael Andrew

    2013-01-01

    The JC polyoma viral coat protein VP1 was analyzed for amino acid sequences homologies to the IDSP sequence which mediates binding of VLA-4 (integrin alpha 4) to vascular cell adhesion molecule 1. Although the full sequence was not found, a DSP sequence was located near the critical arginine residue linked to infectivity of the virus and binding to sialic acid containing molecules such as integrins (3). For the JC polyoma virus, a DSP sequence was found at residues 70, 71 and 72 with homology also noted for the mouse polyoma virus and SV40 virus. Three dimensional modeling of the VP1 molecule suggests that the DSP loop has an accessible site for interaction from the external side of the assembled viral capsid pentamer.

  7. Platelet-endothelial cell adhesion molecule-1 (PECAM-1/CD31) tyrosine phosphorylation state changes during vasculogenesis in the murine conceptus.

    PubMed Central

    Pinter, E.; Barreuther, M.; Lu, T.; Imhof, B. A.; Madri, J. A.

    1997-01-01

    Vasculogenesis, the differentiation of mesodermal cells to angioblasts and the subsequent formation of blood islands and blood vessels by angioblasts in the conceptus, is a dynamic process modulated, in part, by cell-extracellular matrix and cell-cell interactions in the presence of a variety of growth factors and morphogens. In this report we demonstrate differential tyrosine phosphorylation of platelet-endothelial cell adhesion molecule-1 (PECAM-1) during the formation of blood islands and vessels from clusters of extraembryonic and embryonic angioblasts in the murine conceptus. In addition, we identify the phosphorylation of a particular tyrosine residue in the PECAM-1 cytoplasmic domain, Tyr686, which has the potential of mediating binding to Src homology 2 domain-containing proteins, affecting PECAM-1 cellular localization and endothelial cell migration. Images Figure 1 Figure 2 Figure 3 PMID:9137078

  8. Circulating intercellular cell adhesion molecule-1, endothelin-1 and von Willebrand factor-markers of endothelial dysfunction in uncomplicated essential hypertension: the effect of treatment with ACE inhibitors.

    PubMed

    Hlubocká, Z; Umnerová, V; Heller, S; Peleska, J; Jindra, A; Jáchymová, M; Kvasnicka, J; Horký, K; Aschermann, M

    2002-08-01

    The aim of the study was to examine whether the circulating cell adhesion molecules, von Willebrand factor (vWf) and endothelin-1, are elevated in patients with essential hypertension with no other risk factors for atherosclerosis and thus may serve as a markers of endothelial dysfunction in uncomplicated hypertension. Furthermore, the effect of treatment with the ACE inhibitor, quinapril, on levels of endothelial dysfunction markers were studied. The levels of adhesion molecules (intercellular cell adhesion molecule-1 [ICAM-1], E-selectin, P-selectin), von Willebrand factor (vWf) and endothelin-1 were measured in patients with hypertension without any other risk factors of atherosclerosis before and after treatment with quinapril (n = 22) and in normotensive controls (n = 22). Compared with normotensive subjects, the hypertensive patients had significantly higher levels of ICAM-1 (238 vs 208 ng/ml, P = 0.02), vWf (119 vs 105 IU/dl, P < 0.05) and endothelin-1 (5.76 vs 5.14 fmol/ml, P < 0.05). Three-month treatment of hypertensive patients with quinapril led to a significant decrease in the levels of endothelin-1 (5.76 vs 5.28 fmol/ml, P < 0.01). We did not observe significant changes in the levels of adhesion molecules and vWf after ACE inhibitor treatment, although a trend toward a decrease was apparent with all these parameters. Patients with uncomplicated hypertension with no other risk factors of atherosclerosis had significantly elevated levels of ICAM-1, vWf, and endothelin-1. Our data suggest that these factors may serve as markers of endothelial damage even in uncomplicated hypertension. In hypertensive patients, treatment with the ACE inhibitor quinapril resulted in a significant decrease in endothelin-1 levels. These findings indicate a beneficial effect of ACE inhibitors on endothelial dysfunction in hypertensive patients.

  9. Chinese Herbal Cardiotonic Pill Stabilizes Vulnerable Plaques in Rabbits by Decreasing the Expression of Adhesion Molecules

    PubMed Central

    Chen, Liang; Li, Xiaonan; Li, Changjiang; Rong, Yuanyuan; Xiao, Yawei; Xu, Xinsheng; Yao, Guihua; Jiang, Guihua

    2016-01-01

    Abstract: The cardiotonic pill (CP), consisting of a mixture of Radix Salviae Miltiorrhizae, Radix Notoginseng, and Borneolum Syntheticum, has been widely used in the prevention and treatment of cardiovascular disease. Adhesion molecules, including intercellular cell adhesion molecule-1 and vascular cell adhesion molecule-1, are involved in the development of vulnerable plaque. We investigated the effect of the CP in a rabbit model of vulnerable plaque established by local transfection with p53 gene. Compared with the control group, rabbits with vulnerable plaque showed a significantly lower intima-media thickness and plaque burden after CP treatment for 12 weeks. Moreover, the reduction in rate of plaque rupture and vulnerability index was similar. On enzyme-linked immunosorbent assay, real-time polymerase chain reaction, and immunohistochemistry analysis, the expression of intercellular cell adhesion molecule-1 and vascular cell adhesion molecule-1 was inhibited with CP treatment. CP treatment could postpone atherosclerotic plaque development and stabilize vulnerable plaque by inhibiting the expression of adhesion molecules in treatment of cardiovascular disease. PMID:27110743

  10. [Effects of cigarette smoke exposure on pulmonary vascular intercellular adhesion molecule-1 and matrix metalloproteinase-9 in rats].

    PubMed

    Hu, Xiao-Yun; Zhang, Hong-Li; Xu, Jian-Ying; Wang, Chen

    2009-09-01

    To understand the effects of cigarette smoke exposure and smoke cessation on the structure, inflammation and remodeling of pulmonary blood vessels in rats. Thirty-two male Wistar rats were randomly divided into a control group, a smoke exposure group 1 (low dose smoke), a smoke exposure group 2 (high dose smoke) and a smoke cessation group, with 8 rats in each group. The ratio of pulmonary vascular wall thickness/vascular external diameter (WT%) and the ratio of pulmonary vascular wall area/total pulmonary vascular area (WA%) were measured by the image analysis system. The expressions of pulmonary vascular ICAM-1 and MMP-9 protein and mRNA were detected respectively by enzyme linked immunosorbent assay (ELISA) and in situ hybridization techniques. WT% and WA% increased significantly in the smoke exposure group 1 [(15.3 +/- 2.1)%, (41 +/- 7)%] and smoke exposure group 2 [(18.0 +/- 2.0)%, (50 +/- 7)%] compared to those of the control group [(10.4 +/- 2.0)%, (30 +/- 4)%] (q = 4.93 - 11.16, P < 0.05, respectively). The WT% and WA% in the smoke cessation group [(11.0 +/- 1.3)%, (35 +/- 5)%] decreased significantly compared to those of the smoke exposure group 2 (q = 6.74 - 10.29, P < 0.05, respectively). The expression of pulmonary vascular ICAM-1 protein and mRNA increased significantly in the smoke cessation group, the smoke exposure group 1 and the smoke exposure group 2 [(7.9 +/- 3.2 and 6.2 +/- 3.0), (12.9 +/- 2.3 and 10.3 +/- 2.2), (19.2 +/- 2.3 and 18.3 +/- 2.4)] compared to those of the control group (4.7 +/- 2.3 and 2.7 +/- 1.7) (q = 3.28 - 15.76, P < 0.05, respectively). However, the expression of ICAM-1 protein and mRNA was lower in the smoke cessation group compared to those of the smoke exposure groups (q = 3.85 - 12.46, P < 0.05, respectively). The expression of MMP-9 protein and mRNA increased significantly in the smoke cessation group, smoke exposure group 1 and smoke exposure group 2 [(12.0 +/- 2.8 and 7.0 +/- 3.4), (16.1 +/- 2.8 and 12.5 +/- 1.8), (22

  11. Tocotrienol is the most effective vitamin E for reducing endothelial expression of adhesion molecules and adhesion to monocytes.

    PubMed

    Theriault, Andre; Chao, Jun-Tzo; Gapor, Abdul; Chao, Jun Tzo; Gapor, Abeli

    2002-01-01

    Alpha-tocopherol and its esterified derivatives have been shown to be effective in reducing monocytic-endothelial cell adhesion. However, the effect of alpha-tocotrienol (alpha-T3) has not been characterized. In the present study, using human umbilical vein endothelial cells (HUVEC) as the model system, we examined the relative inhibitory effects of alpha-T3 and other vitamin E derivatives on cell surface adhesion molecule expression under TNF-alpha stimulation. Using enzyme-linked immunosorbent assay, we demonstrated that alpha-T3 markedly inhibited the surface expression of vascular cell adhesion molecule-1 in TNF-alpha activated HUVEC in a dose- and time-dependent manner. The optimal inhibition was observed at 25 micromol/l alpha-T3 within 24 h (77+/-5%) without cytotoxicity. In addition, the surface expression of intercellular adhesion molecule-1 and E-selectin were also reduced by 40+/-7 and 42+/-5%, respectively. In order to further evaluate the effects of alpha-T3 on the vascular endothelium, we investigated the ability of monocytes to adhere to endothelial cells. Interestingly, a 63+/-3% decrease in monocytic cell adherence was observed. Compared to alpha-tocopherol and alpha-tocopheryl succinate, alpha-T3 displayed a more profound inhibitory effect on adhesion molecule expression and monocytic cell adherence. This inhibitory action by alpha-T3 on TNF-alpha-induced monocyte adhesion was shown to be NF-kappaB dependent and was interestingly reversed with co-incubation with farnesol and geranylgeraniol, suggesting a role for prenylated proteins in the regulation of adhesion molecule expression. In summary, the above results suggest that alpha-T3 is a potent and effective agent in the reduction of cellular adhesion molecule expression and monocytic cell adherence.

  12. Change in platelet endothelial cell adhesion molecule-1 immunoreactivity in the dentate gyrus in gerbils fed a folate-deficient diet.

    PubMed

    Yoo, Ki-Yeon; Hwang, In Koo; Kim, Young Sup; Kwon, Dae Young; Won, Moo Ho

    2008-02-01

    Folate deficiency increases stroke risk. We examined whether folate deficiency affects platelet endothelial cell adhesion molecule-1 (PECAM-1), which is an immunoglobulin-associated cell adhesion molecule and mediates the final common pathway of neutrophil transendothelial migration, in blood vessels in the gerbil dentate gyrus after transient forebrain ischemia. Gerbils were exposed to a folic acid-deficient diet (FAD) for 3 months and then subjected to common carotid artery occlusion for 5 min. In the control diet (CD)- and FAD-treated sham-operated groups, weak PECAM-1 immunoreactivity was detected in the blood vessels located in the dentate gyrus. PECAM-1 immunoreactivity in both groups was increased by 4 days after ischemic insult. PECAM-1 immunoreactivity in the FAD-treated group was twice as high that in the CD-treated-sham-operated group 4 days after ischemic insult. Western blot analyses showed that the change patterns in PECAM-1 protein levels in the dentate gyrus in both groups after ischemic insult were similar to changes in PECAM-1 immunohistochemistry in the ischemic dentate gyrus. Our results suggest that folate deficiency enhances PECAM-1 in the dentate gyrus induced by transient ischemia.

  13. An anti-platelet-endothelial cell adhesion molecule-1 antibody inhibits leukocyte extravasation from mesenteric microvessels in vivo by blocking the passage through the basement membrane

    PubMed Central

    1996-01-01

    Platelet-endothelial cell adhesion molecule-1 (PECAM-1, CD31) plays an active role in the process of leukocyte migration through cultured endothelial cells in vitro and anti-PECAM-1 antibodies (Abs) inhibit accumulation of leukocytes into sites of inflammation in vivo. Despite the latter, it is still not clear at which stage of leukocyte emigration in vivo PECAM-1 is involved. To address this point directly, we studied the effect of an anti-PECAM-1 Ab, recognizing rat PECAM-1, on leukocyte responses within rat mesenteric microvessels using intravital microscopy. In mesenteric preparations activated by interleukin (IL)-1 beta, the anti-PECAM-1 Ab had no significant effect on the rolling or adhesion of leukocytes, but inhibited their migration into the surrounding extravascular tissue in a dose-dependent manner. Although in some vessel segments these leukocytes had come to a halt within the vascular lumen, often the leukocytes appeared to be trapped within the vessel wall. Analysis of these sections by electron microscopy revealed that the leukocytes had passed through endothelial cell junctions but not the basement membrane. In contrast to the effect of the Ab in mesenteric preparations treated with IL-1 beta, leukocyte extravasation induced by topical or intraperitoneal administration of the chemotactic peptide formyl-methionyl-leucyl-phenylalanine was not inhibited by the anti-PECAM-1 Ab. These results directly demonstrate a role for PECAM-1 in leukocyte extravasation in vivo and indicate that this involvement is selective for leukocyte extravasation elicited by certain inflammatory mediators. Further, our findings provide the first in vivo indication that PECAM-1 may have an important role in triggering the passage of leukocytes through the perivascular basement membrane. PMID:8691137

  14. Elevation of soluble intercellular adhesion molecule-1 levels, but not angiopoietin 2, in the plasma of human immunodeficiency virus-infected African women with clinical Kaposi sarcoma.

    PubMed

    Graham, Susan M; Rajwans, Nimerta; Richardson, Barbra A; Jaoko, Walter; McClelland, R Scott; Overbaugh, Julie; Liles, W Conrad

    2014-10-01

    Circulating levels of endothelial activation biomarkers are elevated in during infection with human immunodeficiency virus 1 (HIV-1) and may also be increased in Kaposi sarcoma (KS). We compared 23 HIV-1-seropositive women with clinically diagnosed KS with 46 randomly selected controls matched for visit year, CD4 count, and antiretroviral therapy status. Conditional logistic regression was used to identify differences between cases and controls. The odds of clinical KS increased with increasing plasma viral load and with intercellular adhesion molecule 1 (ICAM-1) levels above or equal to the median. There was a borderline association between increasing plasma angiopoietin 2 levels and KS. In multivariable modeling including plasma viral load, angiopoietin 2, and ICAM-1, plasma ICAM-1 levels above or equal to the median remained associated with clinical KS (odds ratio = 14.2, 95% confidence interval = 2.3-87.7). Circulating ICAM-1 levels should be evaluated as a potential biomarker for disease progression and treatment response among HIV-infected KS patients.

  15. Effects of alpha-tocopherol on superoxide production and plasma intercellular adhesion molecule-1 and antibodies to oxidized LDL in chronic smokers.

    PubMed

    van Tits, L J; de Waart, F; Hak-Lemmers, H L; van Heijst, P; de Graaf, J; Demacker, P N; Stalenhoef, A F

    2001-05-15

    Antioxidants have been postulated to exert beneficial effects in atherosclerosis. Atherosclerosis is associated with raised plasma levels of soluble intercellular adhesion molecule-1 (sICAM-1) and autoantibodies against oxidized low-density lipoprotein (oxLDL). It is not known whether antioxidants affect these plasma factors in chronic smokers. In a randomized double-blind placebo-controlled study involving 128 male normolipidemic chronic smokers the effect of a 2-year alpha-tocopherol treatment (400 IU dL-alpha-tocopherol daily) on plasma levels of sICAM-1 and autoantibodies against oxLDL was evaluated. In addition, we monitored production of superoxide by leukocytes ex vivo. It was found that compared to nonsmokers (n = 33) plasma levels of IgG but not IgM autoantibodies against oxLDL and concentrations of sICAM-1 in smokers were significantly elevated (30 and 42%, respectively). After supplementation with alpha-tocopherol concentration of TBARS in plasma and in vitro oxidizability of LDL had decreased, but autoantibodies and sICAM-1 had not changed. Production of superoxide was not different between alpha-tocopherol- and placebo-treated smokers. It is concluded that in chronic smokers, long-term treatment with alpha-tocopherol does not normalize the raised levels of sICAM-1 and autoantibodies against oxLDL, both risk factors for initiation or progression of cardiovascular disease, despite a decrease in in vitro oxidizability of LDL.

  16. Correlation of serum intercellular adhesion molecule 1 and vascular endothelial growth factor with tumor grading and staging in breast cancer patients.

    PubMed

    Haghi, Alireza Rastgoo; Vahedi, Amir; Shekarchi, Ali Akbar; Kamran, Aziz

    2017-01-01

    Breast cancer is the most common cancer among women. There are several prognostic factors for this disease. The aim of this article is to explore the correlation of serum level of vascular endothelial growth factor (VEGF) and intercellular adhesion molecule 1 (ICAM1) with tumor, node, metastasis staging and grading of breast cancer. Serum samples of 51 patients with breast cancer were assessed with enzyme-linked immunosorbent assay for the level of VEGF and ICAM1 preoperatively. After the operation, histopathologic specimens stained with hematoxylin and eosin were evaluated for tumor size, histopathologic subtype, grade, lymph node, vascular and lymphatic involvement. Then, the correlation of tumor stage and grade and serum level of markers was analyzed. There was no significant correlation between serum level of markers with vascular invasions, lymph node involvement, and menstruation. There was a weak correlation between tumor size and serum level of ICAM1 with Pearson score correlation, but there was no significant correlation with VEGF. There was no significant correlation between tumor grading and staging with the level of markers. There was a significant correlation between the level of VEGF and ICAM1 and histologic type of tumors in invasive through in situ tumors. Levels of VEGF and ICAM1 can be used as a predictor of tumor invasion and also for target therapy.

  17. Intercellular adhesion molecule-1 polymorphisms, K469E and G261R and susceptibility to vasculitis and rheumatoid arthritis: a meta-analysis.

    PubMed

    Lee, Y H; Bae, S-C

    2016-10-31

    The aim of this study was to determine whether intercellular adhesion molecule-1 (ICAM-1) polymorphisms are associated with susceptibility to vasculitis or rheumatoid arthritis (RA). Meta-analyses were performed to assess the associations between K469E and G241R polymorphisms of ICAM-1 and vasculitis or RA. A total of 12 studies on 1,368 patients and 1,922 controls, which comprised 8 vasculitis studies and 4 RA studies, were included in the meta-analysis. We found no significant association between vasculitis and K469E E allele among the various subjects (OR = 1.238, 95% CI = 0.9781-1.566, p = 0.076). However, an association between vasculitis and K469E polymorphism was observed under homozygote contrast (OR = 1.443, 95% CI = 1.084-1.920, p = 0.012). Stratification by ethnicity and vasculitis type showed no association between vasculitis and 1 K469E polymorphism under heterozygote contrast. In addition, the meta-analysis revealed a significant association between the ICAM-1 G241R R allele and Behcet's disease (BD) (OR = 3.261, 95% CI = 1.653-6.434, p = 0.001), but not giant cell arteritis. Moreover, the meta-analysis indicated an association between RA and the R allele and RR+ RG genotype of the ICAM-1 G241R polymorphism (OR = 2.014, 95% CI = 1.215-3.339, p = 0.007; OR = 2.394, 95% CI = 1.354-4.235, p = 0.003). This meta-analysis suggests that the K469E polymorphism is associated with susceptibility to vasculitis, and that the G241R polymorphism is associated with susceptibility to BD and RA.

  18. Serum Interleukin-18, Fetuin-A, Soluble Intercellular Adhesion Molecule-1, and Endothelin-1 in Ankylosing Spondylitis, Psoriatic Arthritis, and SAPHO Syndrome.

    PubMed

    Przepiera-Będzak, Hanna; Fischer, Katarzyna; Brzosko, Marek

    2016-08-03

    To examine serum interleukin 18 (IL-18), fetuin-A, soluble intercellular adhesion molecule-1 (sICAM-1), and endothelin-1 (ET-1) levels in ankylosing spondylitis (AS), psoriatic arthritis (PsA), and Synovitis Acne Pustulosis Hyperostosis Osteitis syndrome (SAPHO). We studied 81 AS, 76 PsA, and 34 SAPHO patients. We measured serum IL-18, fetuin-A, sICAM-1, ET-1, IL-6, IL-23, vascular endothelial growth factor (VEGF), and epidermal growth factor (EGF). IL-18 levels were higher in AS (p = 0.001), PsA (p = 0.0003), and SAPHO (p = 0.01) than in controls, and were positively correlated with CRP (p = 0.03), VEGF (p = 0.03), and total cholesterol (TC, p = 0.006) in AS and with IL-6 (p = 0.03) in PsA. Serum fetuin-A levels were lower in AS (p = 0.001) and PsA (p = 0.001) than in controls, and negatively correlated with C-reactive protein (CRP) in AS (p = 0.04) and SAPHO (p = 0.03). sICAM-1 positively correlated with CRP (p = 0.01), erythrocyte sedimentation rate (ESR, p = 0.01), and IL-6 (p = 0.008) in AS, and with IL-6 (p = 0.001) in SAPHO. Serum ET-1 levels were lower in AS (p = 0.0005) than in controls. ET-1 positively correlated with ESR (p = 0.04) and Disease Activity Score 28 (DAS28, p = 0.003) in PsA. In spondyloarthritis, markers of endothelial function correlated with disease activity and TC.

  19. Cyclic stretching of mesangial cells up-regulates intercellular adhesion molecule-1 and leukocyte adherence: a possible new mechanism for glomerulosclerosis.

    PubMed

    Riser, B L; Varani, J; Cortes, P; Yee, J; Dame, M; Sharba, A K

    2001-01-01

    Intraglomerular hypertension is a primary causal factor in the progressive glomerulosclerosis that characterizes diabetic nephropathy or severe renal ablation. However, inflammation of the glomerular mesangium also participates in at least the early phase of these diseases. In glomerulonephritis, where inflammation is thought to be the predominant causal factor, intraglomerular hypertension is also often present. Mesangial cells (MCs) are critical in orchestrating key functions of the glomerulus including extracellular matrix metabolism, cytokine production, and interaction with leukocytes. Because MCs are subject to increased stretching when intraglomerular hypertension is present, and in glomerulonephritis MC/leukocyte interactions seem to be mediated primarily via the up-regulation of intercellular adhesion molecule-1 (ICAM-1), we examine the possibility that cyclic stretching is a stimulus for increased MC ICAM-1 activity. We demonstrate that the normal low levels of MC ICAM-1 mRNA and protein are dramatically up-regulated by even short intervals of cyclic stretch. This effect is dose- and time-dependent, and requires little amplitude and a brief period of elongation for significant induction. Stretch-induced MC ICAM-1 also leads to a marked elevation in phagocytic leukocyte adherence. This stimulated adherence is equal or greater than that induced by the inflammatory cytokine tumor necrosis factor-alpha, whereas an additive effect occurs when both are applied in combination. Our results indicate that stretch-induced ICAM-1 may provide a direct link between hypertension and inflammation in the progression of injury and glomerulosclerosis in diabetes, renal ablation, and other forms of glomerulonephritis.

  20. Vitamin E supplementation reduces plasma vascular cell adhesion molecule-1 and von Willebrand factor levels and increases nitric oxide concentrations in hypercholesterolemic patients.

    PubMed

    Desideri, Giovambattista; Marinucci, Maria Contina; Tomassoni, Gianluca; Masci, Pier Giorgio; Santucci, Anna; Ferri, Claudio

    2002-06-01

    Up-regulation of vascular cell adhesion molecule-1 (VCAM-1) and reduced nitric oxide (NO) availability represent early characteristics of atherosclerosis. To evaluate whether the antioxidant vitamin E affected the circulating levels of soluble VCAM-1 (sVCAM-1) and the plasma metabolite of NO (nitrite+nitrate) in hypercholesterolemic patients, either vitamin E (either 400 IU or 800 IU/d for 8 wk) or placebo were randomly, double-blindly given to 36 hypercholesterolemic patients and 22 age- and sex-matched controls. At baseline hypercholesterolemic patients showed higher plasma sVCAM-1 (microg.liter(-1)) (591.2 +/- 132.5 vs. 505.0 +/- 65.6, P < 0.007) and lower NO metabolite (microM) levels (15.9 +/- 3.4 vs. 29.2 +/- 5.1, P < 0.0001) than controls. In hypercholesterolemic patients, 8 wk vitamin E (but not placebo) treatment significantly decreased circulating sVCAM-1 levels (400 IU: -148.9 +/- 84.6, P < 0.009; 800 IU: -204.0 +/- 75.7, P < 0.0001; placebo: -4.7 +/- 22.6, NS), whereas it increased NO metabolite concentrations (400 IU: +4.0 +/- 1.7, P < 0.02; 800 IU: +5.5 +/- 0.8, P < 0.0001; placebo: +0.1 +/- 1.1, NS) without affecting circulating low- density lipoprotein levels. Changes in both plasma sVCAM-1 and NO metabolite levels showed a trend to significantly correlate (r = -0.515, P = 0.010; and r = 0.435, P = 0.034, respectively) with changes in vitamin E concentrations induced by vitamin E supplementation. In conclusion, isolated hypercholesterolemia both increased circulating sVCAM-1 and reduced NO metabolite concentrations. Vitamin E supplementation counteracts these alterations, thus representing a potential tool for endothelial protection in hypercholesterolemic patients.

  1. Folic acid deficiency increases delayed neuronal death, DNA damage, platelet endothelial cell adhesion molecule-1 immunoreactivity, and gliosis in the hippocampus after transient cerebral ischemia.

    PubMed

    Hwang, In Koo; Yoo, Ki-Yeon; Suh, Hong-Won; Kim, Young Sup; Kwon, Dae Young; Kwon, Young-Guen; Yoo, Jun-Hyun; Won, Moo-Ho

    2008-07-01

    Folic acid deficiency increases stroke risk. In the present study, we examined whether folic acid deficiency enhances neuronal damage and gliosis via oxidative stress in the gerbil hippocampus after transient forebrain ischemia. Animals were exposed to a folic acid-deficient diet (FAD) for 3 months and then subjected to occlusion of both common carotid arteries for 5 min. Exposure to an FAD increased plasma homocysteine levels by five- to eightfold compared with those of animals fed with a control diet (CD). In CD-treated animals, most neurons were dead in the hippocampal CA1 region 4 days after ischemia/reperfusion, whereas, in FAD-treated animals, this occurred 3 days after ischemia/reperfusion. Immunostaining for 8-hydroxy-2'-deoxyguanosine (8-OHdG) was performed to examine DNA damage in CA1 neurons in both groups after ischemia, and it was found that 8-OHdG immunoreactivity in both FAD and CD groups peaked at 12 hr after reperfusion, although the immunoreactivity in the FAD group was much greater than that in the CD group. Platelet endothelial cell adhesion molecule-1 (PECAM-1; a final mediator of neutrophil transendothelial migration) immunoreactivity in both groups increased with time after ischemia/reperfusion: Its immunoreactivity in the FAD group was much higher than that in the CD group 3 days after ischemia/reperfusion. In addition, reactive gliosis in the ischemic CA1 region increased with time after ischemia in both groups, but astrocytosis and microgliosis in the FAD group were more severe than in the CD group at all times after ischemia. Our results suggest that folic acid deficiency enhances neuronal damage induced by ischemia. 2008 Wiley-Liss, Inc.

  2. Serum Interleukin-18, Fetuin-A, Soluble Intercellular Adhesion Molecule-1, and Endothelin-1 in Ankylosing Spondylitis, Psoriatic Arthritis, and SAPHO Syndrome

    PubMed Central

    Przepiera-Będzak, Hanna; Fischer, Katarzyna; Brzosko, Marek

    2016-01-01

    To examine serum interleukin 18 (IL-18), fetuin-A, soluble intercellular adhesion molecule-1 (sICAM-1), and endothelin-1 (ET-1) levels in ankylosing spondylitis (AS), psoriatic arthritis (PsA), and Synovitis Acne Pustulosis Hyperostosis Osteitis syndrome (SAPHO). We studied 81 AS, 76 PsA, and 34 SAPHO patients. We measured serum IL-18, fetuin-A, sICAM-1, ET-1, IL-6, IL-23, vascular endothelial growth factor (VEGF), and epidermal growth factor (EGF). IL-18 levels were higher in AS (p = 0.001), PsA (p = 0.0003), and SAPHO (p = 0.01) than in controls, and were positively correlated with CRP (p = 0.03), VEGF (p = 0.03), and total cholesterol (TC, p = 0.006) in AS and with IL-6 (p = 0.03) in PsA. Serum fetuin-A levels were lower in AS (p = 0.001) and PsA (p = 0.001) than in controls, and negatively correlated with C-reactive protein (CRP) in AS (p = 0.04) and SAPHO (p = 0.03). sICAM-1 positively correlated with CRP (p = 0.01), erythrocyte sedimentation rate (ESR, p = 0.01), and IL-6 (p = 0.008) in AS, and with IL-6 (p = 0.001) in SAPHO. Serum ET-1 levels were lower in AS (p = 0.0005) than in controls. ET-1 positively correlated with ESR (p = 0.04) and Disease Activity Score 28 (DAS28, p = 0.003) in PsA. In spondyloarthritis, markers of endothelial function correlated with disease activity and TC. PMID:27527149

  3. The Serum Changes of Neuron-Specific Enolase and Intercellular Adhesion Molecule-1 in Patients With Diffuse Axonal Injury Following Progesterone Administration: A Randomized Clinical Trial

    PubMed Central

    Shahrokhi, Nader; Soltani, Zahra; Khaksari, Mohammad; Karamouzian, Saeid; Mofid, Behshad; Asadikaram, Gholamreza

    2016-01-01

    Background Improvement of neurologic outcome in progesterone-administered patients with diffuse axonal injury (DAI) has been found in a recent study. Also, there has been interest in the importance of serum parameters as predictors of outcome in traumatic brain injury. Objectives The aim of this study was to examine the effect of progesterone administration on serum levels of neuron-specific enolase (NSE), and intercellular adhesion molecule-1 (ICAM-1) in clinical DAI. Patients and Methods In this study, the serum levels of ICAM-1 and NSE of 32 male DAI patients (18 - 60 years of age, a Glasgow coma scale of 12 or less, and admitted within 4 hours after injury) who were randomized for a controlled phase II trial of progesterone were analyzed. The analysis was performed between the control and progesterone groups at admission time, and 24 hours and six days after DAI, respectively. Results A reduction in the serum level of ICAM-1 was noticed in the progesterone group 24 hours after the injury (P < 0.05). There was no significant difference in the serum level of NSE between the study groups during evaluation. At 24 hours after the injury, the level of ICAM-1 in the control group was higher than that at admission time (P < 0.05). The lowest level of NSE in the two groups was seen six days after DAI (P < 0.01). Conclusions In summary, progesterone administration reduced serum ICAM-1, and whereby may attenuate blood brain barrier disruption, the latter needs further investigation for confirmation. PMID:27800469

  4. Ursolic acid, a natural pentacyclic triterpenoid, inhibits intracellular trafficking of proteins and induces accumulation of intercellular adhesion molecule-1 linked to high-mannose-type glycans in the endoplasmic reticulum

    PubMed Central

    Mitsuda, Satoshi; Yokomichi, Tomonobu; Yokoigawa, Junpei; Kataoka, Takao

    2014-01-01

    Ursolic acid (3β-hydroxy-urs-12-en-28-oic acid) is a natural pentacyclic triterpenoid that is present in many plants, including medicinal herbs, and foods. Ursolic acid was initially identified as an inhibitor of the expression of intercellular adhesion molecule-1 (ICAM-1) in response to interleukin-1α (IL-1α). We report here a novel biological activity: ursolic acid inhibits intracellular trafficking of proteins. Ursolic acid markedly inhibited the IL-1α-induced cell-surface ICAM-1 expression in human cancer cell lines and human umbilical vein endothelial cells. By contrast, ursolic acid exerted weak inhibitory effects on the IL-1α-induced ICAM-1 expression at the protein level. Surprisingly, we found that ursolic acid decreased the apparent molecular weight of ICAM-1 and altered the structures of N-linked oligosaccharides bound to ICAM-1. Ursolic acid induced the accumulation of ICAM-1 in the endoplasmic reticulum, which was linked mainly to high-mannose-type glycans. Moreover, in ursolic-acid-treated cells, the Golgi apparatus was fragmented into pieces and distributed over the cells. Thus, our results reveal that ursolic acid inhibits intracellular trafficking of proteins and induces the accumulation of ICAM-1 linked to high-mannose-type glycans in the endoplasmic reticulum. PMID:24649404

  5. Small GTPase Rho signaling is involved in {beta}1 integrin-mediated up-regulation of intercellular adhesion molecule 1 and receptor activator of nuclear factor {kappa}B ligand on osteoblasts and osteoclast maturation

    SciTech Connect

    Hirai, Fumihiko; Nakayamada, Shingo; Okada, Yosuke; Saito, Kazuyoshi; Kurose, Hitoshi; Mogami, Akira; Tanaka, Yoshiya . E-mail: tanaka@med.uoeh-u.ac.jp

    2007-04-27

    We assessed the characteristics of human osteoblasts, focusing on small GTPase Rho signaling. {beta}1 Integrin were highly expressed on osteoblasts. Engagement of {beta}1 integrins by type I collagen augmented expression of intercellular adhesion molecule 1 (ICAM-1) and receptor activator of nuclear factor {kappa}B ligand (RANKL) on osteoblasts. Rho was activated by {beta}1 stimulation in osteoblasts. {beta}1 Integrin-induced up-regulation of ICAM-1 and RANKL was inhibited by transfection with adenoviruses encoding C3 transferase or pretreated with Y-27632, specific Rho and Rho-kinase inhibitors. Engagement of {beta}1 integrin on osteoblasts induced formation of tartrate-resistant acid phosphatase (TRAP)-positive multinuclear cells (MNC) in a coculture system of osteoblasts and peripheral monocytes, but this action was completely abrogated by transfection of C3 transferase. Our results indicate the direct involvement of Rho-mediated signaling in {beta}1 integrin-induced up-regulation of ICAM-1 and RANKL and RANKL-dependent osteoclast maturation. Thus, Rho-mediated signaling in osteoblasts seems to introduce major biases to bone resorption.

  6. Associations of a polymorphism in the intercellular adhesion molecule-1 (ICAM1) gene and ICAM1 serum levels with migraine in a Chinese Han population.

    PubMed

    He, Qiu; Lin, Xiang; Wang, Fengzhi; Xu, Jialiang; Ren, Zhanxiu; Chen, Wei; Xing, Xuesha

    2014-10-15

    To investigate the associations of a polymorphism in the intercellular adhesion molecule-1 (ICAM1) gene, and ICAM1 serum levels, with migraine and migraine subtypes in a Han Chinese population. We used PCR-restriction fragment length polymorphism (PCR-RFLP) and gene sequencing to analyze the genotype and allelic frequencies of the K469E (rs5498) and G241R (rs1799969) ICAM1 polymorphisms between migraine cases and controls. Serum levels of ICAM1 were tested by enzyme linked immunosorbent assay (ELISA). (1) We found significant higher frequencies of the distribution of the E/E genotype and the E allele of the K469E polymorphism between migraine cases and controls (χ(2) = 4.948 &P<0.05 and χ(2) = 13.990 &P<0.01, respectively), and between a migraine without aura subtype of migraine cases and controls (χ(2) = 5.265 &P<0.05; χ(2 )= 20.501 &P<0.01, respectively). After correction by conditional logistical regression, the frequency distribution difference of the E/E genotype between the migraine cases and controls remained statistically significant (OR = 32.85, 95% CI:4.22-28.79, P = 0.007.) (2) ICAM1 serum levels were significantly higher in migraine cases than in controls (P<0.01) and, within migraine cases, were significantly higher in K469E E allele carriers than in K allele carriers (P<0.01). Our data indicate that the E/E genotype of the ICAM1 K469E polymorphism may be an important risk factor for migraine in a Han Chinese population, and that this polymorphism affects ICAM1 serum levels. Although the independent risk factor constituted by this polymorphism in other ethnic groups requires further study, our studies raise the possibility of the development of ICAM1 K469E E allele-specific therapeutics for the prevention and treatment of migraine in the Chinese Han population. Copyright © 2014. Published by Elsevier B.V.

  7. Extracellular matrix proteins matrix metallopeptidase 9 (MMP9) and soluble intercellular adhesion molecule 1 (sICAM-1) and correlations with clinical staging in euthymic bipolar disorder.

    PubMed

    Reininghaus, Eva Z; Lackner, Nina; Birner, Armin; Bengesser, Susanne; Fellendorf, Frederike T; Platzer, Martina; Rieger, Alexandra; Queissner, Robert; Kainzbauer, Nora; Reininghaus, Bernd; McIntyre, Roger S; Mangge, Harald; Zelzer, Sieglinde; Fuchs, Dietmar; Dejonge, Silvia; Müller, Norbert

    2016-03-01

    Matrix metallopeptidase 9 (MMP9) and soluble intercellular adhesion molecule 1 (sICAM-1) are both involved in the restructuring of connective tissues. Evidence also implicates MMP9 and sICAM in cardiovascular and neoplastic diseases, where blood levels may be a marker of disease severity or prognosis. In individuals with bipolar disorder (BD), higher risk for cardiovascular illness has been extensively reported. The aim of this investigation was to measure and compare peripheral levels of serum MMP9 and sICAM in adults with euthymic BD and healthy controls (HC). Furthermore, we focussed on correlations with illness severity and metabolic parameters. MMP9 levels among the BD sample (n = 112) were significantly higher than among the HC (n = 80) (MMP9: F = 9.885, p = 0.002, η(2)  = 0.058) after controlling for confounding factors. Patients with BD in a later, progressive stage of disease showed significantly higher MMP9 as well as sICAM-1 levels compared to patients with BD in an earlier stage of disease (MMP9: F = 5.8, p = 0.018, η(2)  = 0.054; sICAM-1: F = 5.6, p = 0.020, η(2)  = 0.052). Correlation analyses of cognitive measures revealed a negative association between performance on the d2 Test of Attention and MMP9 (r = -0.287, p = 0.018) in the BD sample. Despite the sample being euthymic (i.e., according to conventional criteria) at the time of analysis, we found significant correlations between MMP9 as well as sICAM-1 and subthreshold depressive/hypomanic symptoms. A collection of disparate findings herein point to a role of MMP9 and cICAM-1 in the patho-progressive process of BD: the increased levels of serum MMP9 and sICAM-1, the correlation between higher levels of these parameters, progressive stage, and cognitive dysfunction in BD, and the positive correlation with subthreshold symptoms. As sICAM-1 and MMP9 are reliable biomarkers of inflammatory and early atherosclerotic disease, these markers may provide indications of the

  8. Angiopoietin-1 reduces VEGF-stimulated leukocyte adhesion to endothelial cells by reducing ICAM-1, VCAM-1, and E-selectin expression.

    PubMed

    Kim, I; Moon, S O; Park, S K; Chae, S W; Koh, G Y

    2001-09-14

    Vascular endothelial growth factor (VEGF) and angiopoietin-1 (Ang1) are potent vasculogenic and angiogenic factors that hold promise as a means to produce therapeutic vascularization and angiogenesis. However, VEGF also acts as a proinflammatory cytokine by inducing adhesion molecules that bind leukocytes to endothelial cells, an initial and essential step toward inflammation. In the present study, we used human umbilical vascular endothelial cells (HUVECs) to examine the effect of Ang1 on VEGF-induced expression of three adhesion molecules: intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin. Interestingly, Ang1 suppressed VEGF-induced expression of these adhesion molecules. Furthermore, Ang1 reduced VEGF-induced leukocyte adhesion to HUVECs. These results demonstrate that Ang1 counteracts VEGF-induced inflammation by reducing VEGF-induced endothelial adhesiveness.

  9. Renal cell carcinoma alters endothelial receptor expression responsible for leukocyte adhesion.

    PubMed

    Juengel, Eva; Krueger, Geraldine; Rutz, Jochen; Nelson, Karen; Werner, Isabella; Relja, Borna; Seliger, Barbara; Fisslthaler, Beate; Fleming, Ingrid; Tsaur, Igor; Haferkamp, Axel; Blaheta, Roman A

    2016-04-12

    Renal cell carcinoma (RCC) escapes immune recognition. To elaborate the escape strategy the influence of RCC cells on endothelial receptor expression and endothelial leukocyte adhesion was evaluated. Human umbilical vein endothelial cells (HUVEC) were co-cultured with the RCC cell line, Caki-1, with and without tumor necrosis factor (TNF)-alpha. Intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), endothelial (E)-selectin, standard and variants (V) of CD44 were then analysed in HUVEC, using flow cytometry and Western blot analysis. To determine which components are responsible for HUVEC-Caki-1 interaction causing receptor alteration, Caki-1 membrane fragments versus cell culture supernatant were applied to HUVECS. Adhesion of peripheral blood lymphocytes (PBL) and polymorphonuclear neutrophils (PMN) to endothelium was evaluated by co-culture adhesion assays. Relevance of endothelial receptor expression for adhesion to endothelium was determined by receptor blockage. Co-culture of RCC and HUVECs resulted in a significant increase in endothelial ICAM-1, VCAM-1, E-selectin, CD44 V3 and V7 expression. Previous stimulation of HUVECs with TNF-alpha and co-cultivation with Caki-1 resulted in further elevation of endothelial CD44 V3 and V7 expression, whereas ICAM-1, VCAM-1 and E-selectin expression were significantly diminished. Since Caki-1 membrane fragments also caused these alterations, but cell culture supernatant did not, cell-cell contact may be responsible for this process. Blocking ICAM-1, VCAM-1, E-selectin or CD44 with respective antibodies led to a significant decrease in PBL and PMN adhesion to endothelium. Thus, exposing HUVEC to Caki-1 results in significant alteration of endothelial receptor expression and subsequent endothelial attachment of PBL and PMN.

  10. Up-regulation of tumor suppressor carcinoembryonic antigen-related cell adhesion molecule 1 in human colon cancer Caco-2 cells following repetitive exposure to dietary levels of a polyphenol-rich chokeberry juice.

    PubMed

    Bermúdez-Soto, María J; Larrosa, Mar; Garcia-Cantalejo, Jesús M; Espín, Juan C; Tomás-Barberan, Francisco A; García-Conesa, María T

    2007-04-01

    Consumption of berries and red fruits rich in polyphenols may contribute to the reduction of colon cancer through mechanisms not yet understood. In this study, we investigated the response of subconfluent Caco-2 cells (a human colon carcinoma model) to repetitive exposure (2 h a day for a 4-day period) of a subtoxic dose of a chokeberry (Aronia melanocarpa) juice containing mixed polyphenols. To mimic physiological conditions, we subjected the chokeberry juice to in vitro gastric and pancreatic digestion. The effects on viability, proliferation and cell cycle were determined, and changes in the expression of genes in response to the chokeberry treatment were screened using Affymetrix oligonucleotide microarrays. Exposure to the chokeberry juice inhibited Caco-2 cell proliferation by causing G(2)/M cell cycle arrest. We detected changes in the expression of a group of genes involved in cell growth and proliferation and cell cycle regulation, as well as those associated to colorectal cancer. A selection of these genes was further confirmed by quantitative RT-PCR. Among these, the tumor suppressor carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), whose expression is known to be reduced in the majority of early adenomas and carcinomas, was up-regulated by the treatment both at the mRNA and protein levels (as shown by flow cytometry analysis). CEACAM1, with a significant regulatory role on cell proliferation of particular interest at early stages of cancer development, may be a potential target for chemoprevention by food components such as those present in polyphenol-rich fruits.

  11. Neisserial outer membrane vesicles bind the coinhibitory receptor carcinoembryonic antigen-related cellular adhesion molecule 1 and suppress CD4+ T lymphocyte function.

    PubMed

    Lee, Hannah S W; Boulton, Ian C; Reddin, Karen; Wong, Henry; Halliwell, Denise; Mandelboim, Ofer; Gorringe, Andrew R; Gray-Owen, Scott D

    2007-09-01

    Pathogenic Neisseria bacteria naturally liberate outer membrane "blebs," which are presumed to contribute to pathology, and the detergent-extracted outer membrane vesicles (OMVs) from Neisseria meningitidis are currently employed as meningococcal vaccines in humans. While the composition of these vesicles reflects the bacteria from which they are derived, the functions of many of their constituent proteins remain unexplored. The neisserial colony opacity-associated Opa proteins function as adhesins, the majority of which mediate bacterial attachment to human carcinoembryonic antigen-related cellular adhesion molecules (CEACAMs). Herein, we demonstrate that the Opa proteins within OMV preparations retain the capacity to bind the immunoreceptor tyrosine-based inhibitory motif-containing coinhibitory receptor CEACAM1. When CD4(+) T lymphocytes were exposed to OMVs from Opa-expressing bacteria, their activation and proliferation in response to a variety of stimuli were effectively halted. This potent immunosuppressive effect suggests that localized infection will generate a "zone of inhibition" resulting from the diffusion of membrane blebs into the surrounding tissues. Moreover, it demonstrates that OMV-based vaccines must be developed from strains that lack CEACAM1-binding Opa variants.

  12. The critical role of residues 43R and 44Q of carcinoembryonic antigen cell adhesion molecules-1 in the protection from killing by human NK cells.

    PubMed

    Markel, Gal; Gruda, Raizy; Achdout, Hagit; Katz, Gil; Nechama, Morris; Blumberg, Richard S; Kammerer, Robert; Zimmermann, Wolfgang; Mandelboim, Ofer

    2004-09-15

    The multifunctional carcinoembryonic Ag cell adhesion molecule (CEACAM)1 protein has recently become the focus of intense immunological research. We have previously shown that the CEACAM1 homophilic interactions inhibit the killing activity of NK cells. This novel inhibitory mechanism plays a key role in melanoma immune evasion, inhibition of decidual immune response, and controlling NK autoreactivity in TAP2-deficient patients. These roles are mediated mainly by homophilic interactions, which are mediated through the N-domain of the CEACAM1. The N-domain of the various members of the CEACAM family shares a high degree of similarity. However, it is still unclear which of the CEACAM family members is able to interact with CEACAM1 and what are the amino acid residues that control this interaction. In this study we demonstrate that CEACAM1 interacts with CEACAM5, but not with CEACAM6. Importantly, we provide the molecular basis for CEACAM1 recognition of various CEACAM family members. Sequence alignment reveals a dichotomy among the CEACAM family members: both CEACAM1 and CEACAM5 contain the R and Q residues in positions 43 and 44, respectively, whereas CEACAM3 and CEACAM6 contain the S and L residues, respectively. Mutational analysis revealed that both 43R and 44Q residues are necessary for CEACAM1 interactions. Implications for differential expression of CEACAM family members in tumors are discussed. Copyright 2004 The American Association of Immunologists, Inc.

  13. Mechanistic Control of Carcinoembryonic Antigen-related Cell Adhesion Molecule-1 (CEACAM1) Splice Isoforms by the Heterogeneous Nuclear Ribonuclear Proteins hnRNP L, hnRNP A1, and hnRNP M*

    PubMed Central

    Dery, Kenneth J.; Gaur, Shikha; Gencheva, Marieta; Yen, Yun; Shively, John E.; Gaur, Rajesh K.

    2011-01-01

    Carcinoembryonic antigen-related cell adhesion molecule-1 (CEACAM1) is expressed in a variety of cell types and is implicated in carcinogenesis. Alternative splicing of CEACAM1 pre-mRNA generates two cytoplasmic domain splice variants characterized by the inclusion (L-isoform) or exclusion (S-isoform) of exon 7. Here we show that the alternative splicing of CEACAM1 pre-mRNA is regulated by novel cis elements residing in exon 7. We report the presence of three exon regulatory elements that lead to the inclusion or exclusion of exon 7 CEACAM1 mRNA in ZR75 breast cancer cells. Heterologous splicing reporter assays demonstrated that the maintenance of authentic alternative splicing mechanisms were independent of the CEACAM1 intron sequence context. We show that forced expression of these exon regulatory elements could alter CEACAM1 splicing in HEK-293 cells. Using RNA affinity chromatography, three members of the heterogeneous nuclear ribonucleoprotein family (hnRNP L, hnRNP A1, and hnRNP M) were identified. RNA immunoprecipitation of hnRNP L and hnRNP A1 revealed a binding motif located central and 3′ to exon 7, respectively. Depletion of hnRNP A1 or L by RNAi in HEK-293 cells promoted exon 7 inclusion, whereas overexpression led to exclusion of the variable exon. By contrast, overexpression of hnRNP M showed exon 7 inclusion and production of CEACAM1-L mRNA. Finally, stress-induced cytoplasmic accumulation of hnRNP A1 in MDA-MB-468 cells dynamically alters the CEACAM1-S:CEACAM1:L ratio in favor of the l-isoform. Thus, we have elucidated the molecular factors that control the mechanism of splice-site recognition in the alternative splicing regulation of CEACAM1. PMID:21398516

  14. [Effects of endothelial lipase on mRNA expression of adhesion molecule of human umbilical vascular endothelial cells].

    PubMed

    Fang, Yu-qiang; Huang, Lan; Zhao, Xiao-hui; Yin, Yang-guang; Kang, Hua-li; Deng, Meng-yang

    2007-12-01

    To explore the relationship between human umbilical vascular endothelial cells (HUVECs) and endothelial lipase (EL), and the effect of EL on expression of endothelial cell adhesion molecule (ICAM). HUVECs was treated with tumor necrosis factor-alpha(TNF-alpha) 10 microg/L and the mRNA of adhesion molecules [intercellular adhesion molecule-1 (ICAM-1), vascular cellular adhesion molecule-1 (VCAM-1) and E-selectin] were detected by reverse transcription-polymerase chain reaction (RT-PCR). Then the effect of 50 microg/L anti-endothelial lipase (anti-EL) antibody on the influence of TNF-alpha on these adhesion molecules was observed. After being treated with TNF-alpha, the mRNA of adhesion molecules expressed by HUVECs were significant up-regulated, there was significant difference compared with control group (all P<0.01). These effects of TNF-alpha were significantly abolished by 50 microg/L anti-EL antibody (P<0.05 or P<0.01). EL can affect the expression of adhesion molecules on endothelial cell adhesion molecule. This effect of EL may play a role in the pathophysiologic process in the pathogenesis progress of atherosclerosis.

  15. Impact of celecoxib on soluble intercellular adhesion molecule-1 and soluble e-cadherin concentrations in human colon cancer cell line cultures exposed to phytic acid and TNF-alpha.

    PubMed

    Parfiniewicz, Beata; Pendzich, Joanna; Gruchlik, Arkadiusz; Hollek, Andrzej; Weglarz, Ludmiła

    2012-01-01

    Soluble adhesion molecules such as soluble intercellular adhesion molecules-1 (sICAM-1) and soluble E-cadherin (sE-cadherin) play important role in tumor invasion and the development of metastasis. It was observed that their concentrations in body fluids of patients with colon cancer were elevated. Celecoxib, a selective inhibitor of cyclooxygenase-2 (COX-2) besides its analgesic, anti-inflammatory, and antipyretic activity is able to inhibit development of colon cancer and reduce risk of metastasis. The additional factors, e.g., dietary components in colon cancer, may influence therapeutic effect of drugs, such as cytokines. TNF-alpha (tumor necrosis factor - alpha) is a cytokine, which concentration significantly increases in serum of patients with inflammatory and cancer diseases. The latest studies demonstrate, that phytic acid (IP6), a myo-inositol derivative, abundantly present in high-fiber diets could substantially reduce colon cancer incidence. The aim of the present study was to evaluate the influence of celecoxib on sICAM-1 and sE-cadherin concentrations in transformed epithelial colon cell cultures simultaneously exposed to IP6 and TNF-alpha. Additionally, the adhesion of the exposed cells to collagen I was assessed. HT-29 and Caco-2 cells were cultured in the presence of 50 ng/mL celecoxib, 1.0 mM IP6, and 100 ng/mL TNF-alpha, and their combination: TNF-alpha plus IP6, TNF-alpha plus celecoxib, IP6 plus celecoxib, and TNF-alpha with celecoxib plus IP6, for 96 h. Nonexposed cell line cultures served as controls. Concentrations of sICAM-1 and sE-cadherin were measured in the culture medium by enzyme-linked immunosorbent assay (ELISA) using Quantikine - Human sICAM-1/CD54 Immunoassay and Quantikine-Human sE-Cadherin Immunoassay. All the results obtained were expressed as ng per mL. In the adhesion assay, the cells were incubated with IP6 (0.5, 1.0 and 2.0 mM), TNF-alpha (100 ng/mL), celecoxib (50 ng/mL) and their combination for 90 min. Fluorescence

  16. Phase I and phase II safety and efficacy trial of intercellular adhesion molecule-1 antisense oligodeoxynucleotide (ISIS 2302) for the prevention of acute allograft rejection.

    PubMed

    Kahan, Barry D; Stepkowski, Stanislaw; Kilic, Murat; Katz, Steven M; Van Buren, Charles T; Welsh, Maria S; Tami, Joseph A; Shanahan, William R

    2004-09-27

    ISIS 2302, an antisense oligonucleotide that inhibits the expression of human intercellular adhesion molecule (ICAM)-1, was evaluated in combination with a cyclosporine (CsA)-prednisone (Pred) regimen first in a phase I safety and pharmacokinetic study and then in a phase II assessment of prophylaxis of acute rejection episodes in deceased donor renal allografts. Both phase I and phase II trials were double-blinded and placebo-controlled, including 17 stable and 39 de novo patients, respectively, in time-lagged, ascending-dose regimens. Each study compared the outcomes of 8 alternate-day intravenous infusions of four ISIS 2302 dose levels (0.05, 0.5, 1.0, or 2.0 mg/kg) versus placebo (3:1 ratio). Patients were followed for 34 days (phase I) or 6 months (phase II). All transplant patients were followed for 3 years. ISIS 2302 produced no evident toxicity; a significant, dose-related increase in activated partial thromboplastin time was accompanied by a trend toward a decreased platelet count. ISIS 2302 did not alter the pharmacokinetic behavior of CsA. At 6 months, the rates of acute rejection episodes were 38.1% in the ISIS 2302 group versus 20.0% in the placebo group. Three-year graft survivals were similar. The mean creatinine values at 1, 2, and 3 years for all ISIS dose groups combined versus placebo over 3 years showed no significant differences. ISIS 2302 did not evoke side-effects and produced slightly improved renal function. However, in this pilot study, it did not further reduce the rate of acute rejection episodes or increase graft survival compared to a concentration-controlled CsA-Pred regimen.

  17. Candida albicans stimulates cytokine production and leukocyte adhesion molecule expression by endothelial cells.

    PubMed Central

    Filler, S G; Pfunder, A S; Spellberg, B J; Spellberg, J P; Edwards, J E

    1996-01-01

    Endothelial cells have the potential to influence significantly the host immune response to blood-borne microbial pathogens, such as Candida albicans. We investigated the ability (of this organism to stimulate endothelial cell responses relevant to host defense in vitro. Infection with C. albicans induced endothelial cells to express mRNAs encoding E-selectin, intercellular adhesion molecule 1, vascular cell adhesion molecule 1, interleukin 6, interleukin 8, monocyte chemoattractant protein 1, and inducible cyclooxygenase (cox2). All three leukocyte adhesion molecule proteins were expressed on the surfaces of the endothelial cells after 8 h of exposure to C. albicans. An increase in secretion of all three cytokines was found after 12 h of infection. Cytochalasin D inhibited accumulation of the endothelial cell cytokine and leukocyte adhesion molecule mRNAs in response to C. albicans, suggesting that endothelial cell phagocytosis of the organism is required to induce this response. Live Candida tropicalis, Candida glabrata, a nongerminating strain of C. albicans, and killed C. albicans did not stimulate the expression of any of the cytokine or leukocyte adhesion molecule mRNAs. These findings indicate that a factor associated with live, germinating C. albicans is required for induction of endothelial cell mRNA expression. Furthermore, since endothelial cells phagocytize killed C. albicans, phagocytosis is likely necessary but not sufficient for this organism to stimulate mRNA accumulation. In conclusion, the secretion of proinflammatory cytokines and expression of leukocyte adhesion molecules by endothelial cells in response to C. albicans could enhance the host defense against this organism by contributing to the recruitment of activated leukocytes to sites of intravascular infection. PMID:8698486

  18. ILK mediates LPS-induced vascular adhesion receptor expression and subsequent leucocyte trans-endothelial migration.

    PubMed

    Hortelano, Sonsoles; López-Fontal, Raquel; Través, Paqui G; Villa, Natividad; Grashoff, Carsten; Boscá, Lisardo; Luque, Alfonso

    2010-05-01

    The inflammatory response to injurious agents is tightly regulated to avoid adverse consequences of inappropriate leucocyte accumulation or failed resolution. Lipopolysaccharide (LPS)-activated endothelium recruits leucocytes to the inflamed tissue through controlled expression of membrane-associated adhesion molecules. LPS responses in macrophages are known to be regulated by integrin-linked kinase (ILK); in this study, we investigated the role of ILK in the regulation of the LPS-elicited inflammatory response in endothelium. This study was performed on immortalized mouse endothelial cells (EC) isolated from lung and coronary vasculature. Cells were thoroughly characterized and the role of ILK in the regulation of the LPS response was investigated by suppressing ILK expression using siRNA and shRNA technologies. Phenotypic and functional analyses confirmed that the immortalized cells behaved as true EC. LPS induced the expression of the inflammatory genes E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). ILK knockdown impaired LPS-mediated endothelial activation by preventing the induction of ICAM-1 and VCAM-1. Blockade of the LPS-induced response inhibited the inflammatory-related processes of firm adhesion and trans-endothelial migration of leucocytes. ILK is involved in the expression of cell adhesion molecules by EC activated with the inflammatory stimulus LPS. This reduced expression modulates leucocyte adhesion to the endothelium and the extravasation process. This finding suggests ILK as a potential anti-inflammatory target for the development of vascular-specific treatments for inflammation-related diseases.

  19. Upregulation of Intercellular Adhesion Molecule 1 and Proinflammatory Cytokines by the Major Surface Proteins of Treponema maltophilum and Treponema lecithinolyticum, the Phylogenetic Group IV Oral Spirochetes Associated with Periodontitis and Endodontic Infections

    PubMed Central

    Lee, Sung-Hoon; Kim, Kack-Kyun; Choi, Bong-Kyu

    2005-01-01

    Treponema maltophilum and Treponema lecithinolyticum belong to the group IV oral spirochetes and are associated with endodontic infections, as well as periodontitis. Recently, the genes encoding the major surface proteins (Msps) of these bacteria (MspA and MspTL, respectively) were cloned and sequenced. The amino acid sequences of these proteins showed significant similarity. In this study we analyzed the functional role of these homologous proteins in human monocytic THP-1 cells and primary cultured periodontal ligament (PDL) cells using recombinant proteins. The complete genes encoding MspA and MspTL without the signal sequence were cloned into Escherichia coli by using the expression vector pQE-30. Fusion proteins tagged with N-terminal hexahistidine (recombinant MspA [rMspA] and rMspTL) were obtained, and any possible contamination of the recombinant proteins with E. coli endotoxin was removed by using polymyxin B-agarose. Flow cytometry showed that rMspA and rMspTL upregulated the expression of intercellular adhesion molecule 1 (ICAM-1) in both THP-1 and PDL cells. Expression of proinflammatory cytokines, such as interleukin-6 (IL-6) and IL-8, was also induced significantly in both cell types by the Msps, as determined by reverse transcription-PCR and an enzyme-linked immunosorbent assay, whereas IL-1β synthesis could be detected only in the THP-1 cells. The upregulation of ICAM-1, IL-6, and IL-8 was completely inhibited by pretreating the cells with an NF-κB activation inhibitor, l-1-tosylamido-2-phenylethyl chloromethyl ketone. This suggests involvement of NF-κB activation. The increased ICAM-1 and IL-8 expression in the THP-1 cells obtained with rMsps was not inhibited in the presence of the IL-1 receptor antagonist (IL-1ra), a natural inhibitor of IL-1. Our results show that the Msps of the group IV oral spirochetes may play an important role in amplifying the local immune response by continuous inflammatory cell recruitment and retention at an

  20. Fer and Fps/Fes participate in a Lyn-dependent pathway from FcepsilonRI to platelet-endothelial cell adhesion molecule 1 to limit mast cell activation.

    PubMed

    Udell, Christian M; Samayawardhena, Lionel A; Kawakami, Yuko; Kawakami, Toshiaki; Craig, Andrew W B

    2006-07-28

    Mast cells express the high affinity IgE receptor FcepsilonRI, which upon aggregation by multivalent antigens elicits signals that cause rapid changes within the mast cell and in the surrounding tissue. We previously showed that FcepsilonRI aggregation caused a rapid increase in phosphorylation of both Fer and Fps/Fes kinases in bone marrow-derived mast cells. In this study, we report that FcepsilonRI aggregation leads to increased Fer/Fps kinase activities and that Fer phosphorylation downstream of FcepsilonRI is independent of Syk, Fyn, and Gab2 but requires Lyn. Activated Fer/Fps readily phosphorylate the C terminus of platelet-endothelial cell adhesion molecule 1 (Pecam-1) on immunoreceptor tyrosine-based inhibitory motifs (ITIMs) and a non-ITIM residue (Tyr(700)) in vitro and in transfected cells. Mast cells devoid of Fer/Fps kinase activities display a reduction in FcepsilonRI aggregation-induced tyrosine phosphorylation of Pecam-1, with no defects in recruitment of Shp1/Shp2 phosphatases observed. Lyn-deficient mast cells display a dramatic reduction in Pecam-1 phosphorylation at Tyr(685) and a complete loss of Shp2 recruitment, suggesting a role as an initiator kinase for Pecam-1. Consistent with previous studies of Pecam-1-deficient mast cells, we observe an exaggerated degranulation response in mast cells lacking Fer/Fps kinases at low antigen dosages. Thus, Lyn and Fer/Fps kinases cooperate to phosphorylate Pecam-1 and activate Shp1/Shp2 phosphatases that function in part to limit mast cell activation.

  1. Combined Treatment with Amlodipine and Atorvastatin Calcium Reduces Circulating Levels of Intercellular Adhesion Molecule-1 and Tumor Necrosis Factor-α in Hypertensive Patients with Prediabetes

    PubMed Central

    Huang, Zhouqing; Chen, Chen; Li, Sheng; Kong, Fanqi; Shan, Peiren; Huang, Weijian

    2016-01-01

    Objective: To assess the effect of amlodipine and atorvastatin on intercellular adhesion molecule (ICAM)-1 and tumor necrosis factor (TNF)-α expression, as endothelial function and inflammation indicators, respectively, in hypertensive patients with and without prediabetes. Methods: Forty-five consecutive patients with hypertension, diagnosed according to JNC7, were divided into two groups based on the presence (HD group, n = 23) or absence (H group, n = 22) of prediabetes, diagnosed according to 2010 ADA criteria, including impaired glucose tolerance (IGT) and fasting glucose tests. All patients simultaneously underwent 12-week treatment with daily single-pill amlodipine besylate/atorvastatin calcium combination (5/10 mg; Hisun-Pfizer Pharmaceuticals Co. Ltd). Serum isolated before and after treatment from overnight fasting blood samples was analyzed by ELISA. Results: In the HD and H groups after vs. before 12-week amlodipine/atorvastatin treatment, there were significantly (all P < 0.01) lower levels of ICAM-1 (3.06 ± 0.34 vs. 4.07 ± 0.70 pg/ml; 3.26 ± 0.32 vs. 3.81 ± 0.60 pg/ml, respectively) and TNF-α (78.71 ± 9.19 vs. 110.94 ± 10.71 pg/ml; 80.95 ± 9.33 vs. 101.79 ± 11.72 pg/ml, respectively), with more pronounced reductions in HD vs. H group (ICAM-1Δ: 1.01 ± 0.80 vs. 0.55 ± 0.64 pg/ml, respectively, P = 0.037; TNF-αΔ: 32.23 ± 14.33 vs. 20.84 ± 14.89 pg/ml, respectively, P = 0.011), independent of the blood pressure (BP) and cholesterol level reduction. Conclusions: Amlodipine/atorvastatin improved endothelial function and inflammation, as reflected by lower circulating levels of ICAM-1 and TNF-α, more prominently in hypertensives with than without prediabetes. Starting statin treatment before overt diabetes in hypertensives might thus improve cardiovascular outcomes. PMID:27610083

  2. Adhesion molecule expression in bullous keratopathy.

    PubMed

    Zhu, S N; Nölle, B; Duncker, G

    1996-08-01

    Adhesion molecules may play an important role in the pathogenesis of bullous keratopathy. The expression of the integrin VLA-beta 1, alpha-subunits of the beta 2-integrins LFA-1, Mac-1, and p150,95, the members of the immunoglobulin family ICAM-1 and VCAM-1, and the selectin ELAM-1 on corneas with bullous keratopathy (BK) secondary to intraocular surgery was studied immunohistochemically using an APAAP method. In the corneas with BK (in contrast to normal corneas), a downregulation of VLA-beta 1 was observed throughout the corneal tissues, particularly on the epithelial layer where bullae occurred; ICAM-1 was induced on epithelial membranes in both BK and inflamed corneas; and the expression of beta 2-integrins, VCAM-1 and ELAM-1 was upregulated in some specimens with remaining endothelial cells. The results show that the investigated adhesion molecules may participate in the pathogenesis of BK. The decrease in VLA-beta 1 in patients with BK may be an important factor in the occurrence and development of recurrent bullae; the induced ICAM-1 may recruit beta 2-integrin-positive leukocytes into the epithelial layer, thus aggravating epithelial damage; and beta 2-integrins and VCAM-1 may play a role in endothelial injury and decompensation.

  3. Connexin 43 expressed in endothelial cells modulates monocyte‑endothelial adhesion by regulating cell adhesion proteins.

    PubMed

    Yuan, Dongdong; Sun, Guoliang; Zhang, Rui; Luo, Chenfang; Ge, Mian; Luo, Gangjian; Hei, Ziqing

    2015-11-01

    Adhesion between circulating monocytes and vascular endothelial cells is a key initiator of atherosclerosis. In our previous studies, it was demonstrated that the expression of connexin (Cx)43 in monocytes modulates cell adhesion, however, the effects of the expression of Cx43 in endothelial cells remains to be elucidated. Therefore, the present study investigated the role of the expression of Cx43 in endothelial cells in the process of cell adhesion. A total of four different methods with distinct mechanisms were used to change the function and expression of Cx43 channels in human umbilical vein endothelial cells: Cx43 channel inhibitor (oleamide), enhancer (retinoic acid), overexpression of Cx43 by transfection with pcDNA‑Cx43 and knock‑down of the expression of Cx43 by small interfering RNA against Cx43. The results indicated that the upregulation of the expression of Cx43 enhanced monocyte‑endothelial adhesion and this was markedly decreased by downregulation of Cx43. This mechanism was associated with Cx43‑induced expression of vascular cell adhesion molecule‑1 and intercellular cell adhesion molecule‑1. The effects of Cx43 in endothelial cells was independent of Cx37 or Cx40. These experiments suggested that local regulation of endothelial Cx43 expression within the vasculature regulates monocyte‑endothelial adhesion, a critical event in the development of atherosclerosis and other inflammatory pathologies, with baseline adhesion set by the expression of Cx43. This balance may be crucial in controlling leukocyte involvement in inflammatory cascades.

  4. The effect of inhaled sodium cromoglycate on cellular infiltration into the bronchial mucosa and the expression of adhesion molecules in asthmatics.

    PubMed

    Hoshino, M; Nakamura, Y

    1997-04-01

    There is no direct evidence of the anti-inflammatory effect of inhaled sodium cromoglycate (SCG). To investigate whether inhaled SCG has any effect on cellular infiltration into the bronchial mucosa and the expression of adhesion molecules in patients with asthma, biopsies of the bronchial mucosa were taken from nine patients with atopic bronchial asthma before and after treatment with inhaled SCG (8 mg x day(-1)) from a metered-dose inhaler (MDI). Eosinophils were stained with anti-EG2, neutrophils with anti-NP57, mast cells with anti-AA1, T-lymphocytes with anti-CD4, CD8 and CD3, and macrophages with anti-CD68. Intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), endothelial leucocyte adhesion molecule-1 (ELAM-1) and P-selectin were stained at the same time as adhesion molecules expressed in vascular endothelium. The intensity of ICAM-1 expression in the bronchial epithelium was also evaluated. The numbers of eosinophils, mast cells, T-lymphocytes and macrophages were significantly reduced as a result of SCG administration, and the expression of ICAM-1, VCAM-1 and ELAM-1 was also significantly inhibited. A significant correlation was found between ICAM-1 expression and T-lymphocytes and between VCAM-1 expression and eosinophils. It was concluded that sodium cromoglycate does have an effect on the infiltration of the bronchial mucosa by inflammatory cells and also on the expression of adhesion molecules.

  5. Potential immunosuppressive and antiinflammatory activities of Malaysian medicinal plants characterized by reduced cell surface expression of cell adhesion molecules.

    PubMed

    Tanaka, S; Yoichi, S; Ao, L; Matumoto, M; Morimoto, K; Akimoto, N; Honda, G; Tabata, M; Oshima, T; Masuda, T; bin Asmawi, M Z; Ismail, Z; Yusof, S M; Din, L B; Said, I M

    2001-12-01

    In the search for agents effective against immune-mediated disorders and inflammation, we have screened Malaysian medicinal plants for the ability to inhibit the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) on the surface of murine endothelial cells (F-2), and mouse myeloid leukaemia cells (M1), respectively. Of 41 kinds (29 species, 24 genera, 16 families) of Malaysian plants tested, 10 and 19 plant samples significantly downregulated the expression of ICAM-1 and VCAM-1, respectively. Bioassay-directed fractionation of an extract prepared from the bark of Goniothalamus andersonii showed that its ingredients, goniothalamin (1) and goniodiol (2) inhibited the cell surface expression of both ICAM-1 and VCAM-1. The present results suggest that Malaysian medicinal plants may be abundant natural resources for immunosuppressive and antiinflammatory substances. Copyright 2001 John Wiley & Sons, Ltd.

  6. Comparative study of adhesion molecule expression in nodular lesions of Behçet syndrome and other forms of panniculitis.

    PubMed

    Demirkesen, Cuyan; Tüzüner, Nukhet; Senocak, Mustafa; Türkmen, Iknur; Aki, Hilal; Kepil, Nuray; Mat, Cem; Yazici, Hasan

    2008-07-01

    Adhesion molecules have a role in many vasculitic disorders. Our aim was to evaluate the status of adhesion molecules in nodular lesions of Behçet syndrome (BS) and compare them with results for the 2 most common types of panniculitis, erythema nodosum (EN) and nodular vasculitis (NV). We included the data for 28 patients with nodular lesions of BS, 24 with EN, and 22 with NV. A panel of monoclonal antibodies against E-selectin, P-selectin, vascular cell adhesion molecule-1, platelet endothelial cell adhesion molecule-1, and intercellular adhesion molecule (ICAM)-1 were applied. The distribution and intensity of adhesion molecules were assessed. There were no statistically significant differences between the BS and control groups in regard to these adhesion molecules except for ICAM-1. The percentage of strongly ICAM-1-stained endothelial cells in subcutaneous fat tissue in relation to the total number of endothelial cells was the lowest in BS (P= .0208). Because many lesions of BS were related to an enhanced inflammatory response, the lower percentage of ICAM-1 expression seems counterintuitive.

  7. Expression of adhesion molecules and chemotactic cytokines in cultured human mesothelial cells.

    PubMed

    Jonjić, N; Peri, G; Bernasconi, S; Sciacca, F L; Colotta, F; Pelicci, P; Lanfrancone, L; Mantovani, A

    1992-10-01

    The mesothelium is a flat epithelial lining of serous cavities that could gate the traffic of molecules and cells between the circulation and these body compartments. The present study was designed to elucidate the capacity of mesothelial cells to express adhesion molecules and chemoattractant cytokines, two fundamental mechanisms of regulation of leukocyte recruitment. Cultured human mesothelial cells express appreciable levels of intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1), and these were increased by in vitro exposure to tumor necrosis factor (TNF), interferon gamma (IFN-gamma), or TNF and IFN-gamma. Interleukin 1 (IL-1) was a less consistent stimulus for adhesion molecule expression in vitro. Unlike endothelial cells, used as a reference cell population, resting or stimulated mesothelial cells did not express E-selectin and ICAM-2, as assessed by flow cytometry. Analysis of VCAM-1 mRNA by reverse transcriptase and polymerase chain reaction using appropriate primers revealed that mesothelial cells expressed both the seven- and the six-Ig domain transcripts, with predominance of the longer species. Monocytes bound appreciably to "resting" and, to a greater extent, to stimulated mesothelial cells. Monocytes exposed to IFN-gamma and lipopolysaccharide, used as prototypic activation signals, showed increased capacity to bind mesothelial cells. Anti-CD18 monoclonal antibody significantly inhibited binding of monocytes to mesothelial cells, and this blocking effect was amplified by anti-very late antigen 4. Mesothelial cells were able to express the chemotactic cytokines IL-8 and monocyte chemotactic protein 1 at the mRNA and protein levels. These results indicate that mesothelial cells can express a set of adhesion molecules (ICAM-1 and VCAM-1) overlapping with, but distinct from, that expressed in vascular endothelium (ICAM-1, ICAM-2, VCAM-1, E-selectin), and that these are functionally relevant for interacting with

  8. Inhibition of Adhesion Molecule Gene Expression and Cell Adhesion by the Metabolic Regulator PGC-1α

    PubMed Central

    Minsky, Neri; Roeder, Robert G.

    2016-01-01

    Cell adhesion plays an important role in determining cell shape and function in a variety of physiological and pathophysiological conditions. While links between metabolism and cell adhesion were previously suggested, the exact context and molecular details of such a cross-talk remain incompletely understood. Here we show that PGC-1α, a pivotal transcriptional co-activator of metabolic gene expression, acts to inhibit expression of cell adhesion genes. Using cell lines, primary cells and mice, we show that both endogenous and exogenous PGC-1α down-regulate expression of a variety of cell adhesion molecules. Furthermore, results obtained using mRNA stability measurements as well as intronic RNA expression are consistent with a transcriptional effect of PGC-1α on cell adhesion gene expression. Interestingly, the L2/L3 motifs of PGC-1α, necessary for nuclear hormone receptor activation, are only partly required for inhibition of several cell adhesion genes by PGC-1α. Finally, PGC-1α is able to modulate adhesion of primary fibroblasts and hepatic stellate cells to extracellular matrix proteins. Our results delineate a cross talk between a central pathway controlling metabolic regulation and cell adhesion, and identify PGC-1α as a molecular link between these two major cellular networks. PMID:27984584

  9. Inhibition of Adhesion Molecule Gene Expression and Cell Adhesion by the Metabolic Regulator PGC-1α.

    PubMed

    Minsky, Neri; Roeder, Robert G

    2016-01-01

    Cell adhesion plays an important role in determining cell shape and function in a variety of physiological and pathophysiological conditions. While links between metabolism and cell adhesion were previously suggested, the exact context and molecular details of such a cross-talk remain incompletely understood. Here we show that PGC-1α, a pivotal transcriptional co-activator of metabolic gene expression, acts to inhibit expression of cell adhesion genes. Using cell lines, primary cells and mice, we show that both endogenous and exogenous PGC-1α down-regulate expression of a variety of cell adhesion molecules. Furthermore, results obtained using mRNA stability measurements as well as intronic RNA expression are consistent with a transcriptional effect of PGC-1α on cell adhesion gene expression. Interestingly, the L2/L3 motifs of PGC-1α, necessary for nuclear hormone receptor activation, are only partly required for inhibition of several cell adhesion genes by PGC-1α. Finally, PGC-1α is able to modulate adhesion of primary fibroblasts and hepatic stellate cells to extracellular matrix proteins. Our results delineate a cross talk between a central pathway controlling metabolic regulation and cell adhesion, and identify PGC-1α as a molecular link between these two major cellular networks.

  10. Effects of anti-tumor necrosis factor-alpha and anti-intercellular adhesion molecule-1 antibodies on ischemia/reperfusion lung injury.

    PubMed

    Chiang, Chi-Huei

    2006-10-31

    Inhibition of neutrophil activation and adherence to endothelium by antibodies to tumor necrosis factor-alpha (TNF-alpha) and intercellular adhesion molecules (ICAM-1), respectively, might attenuate ischemia-reperfusion injury (I/R). I/R was conducted in an isolated rat lung model. Anti-TNF-alpha antibody and/or anti-ICAM-1 antibody were added before ischemia or after reperfusion. Hemodynamic changes, lung weight gain (LWG), capillary filtration coefficients (Kfc), and pathologic changes were assessed to evaluate the severity of I/R. The LWG, Kfc, pathological changes and lung injury score of treatment groups with anti-TNF-alpha antibody treatment, either pre-ischemia or during reperfusion, were less than those observed in control groups. Similar findings were found in group treated with anti-ICAM-1 antibody or combination therapy during reperfusion. In contrast, pre-I/R treatment with anti-ICAM-1 antibody induced severe lung edema and failure to complete the experimental procedure. No additional therapeutic effect was found in combination therapy. We conclude that TNF-alpha and ICAM-1 play important roles in I/R. Anti-TNF-alpha antibody has therapeutic and preventive effects on I/R. However, combined therapy with anti-TNF-alpha antibody and anti-ICAM-1 antibody may have no additive effect and need further investigation.

  11. Quantification and localization of HLA-DR and intercellular adhesion molecule-1 (ICAM-1) molecules on bronchial epithelial cells of asthmatics using confocal microscopy.

    PubMed Central

    Vignola, A M; Chanez, P; Campbell, A M; Pinel, A M; Bousquet, J; Michel, F B; Godard, P

    1994-01-01

    An increased expression of HLA-DR and ICAM-1 molecules on bronchial epithelial cells has been observed in asthmatic patients. The aim of this study was to evaluate the localization and to quantify the spontaneous expression of HLA-DR and ICAM-1 on bronchial epithelial cells recovered by bronchial brushing of nine asthmatics and nine controls. Epithelial cells constituted over 95% of cells recovered as shown using an anti-cytokeratin MoAb. Expression of HLA-DR and ICAM-1 was studied using indirect immunofluorescence and confocal microscopy. The intensity of fluorescence of epithelial cells expressing HLA-DR and ICAM-1 was significantly (P < 0.003) increased in asthmatics. In asthmatics, but not in controls, the expression of both molecules was localized in the cytoplasm on the apicolateral portions of the cells. This study shows an up-regulation in the expression of HLA-DR and ICAM-1 molecules by bronchial epithelial cells from asthmatics and a localization of these molecules within the cell. Images Fig. 1 Fig. 1 PMID:7908615

  12. Association Between Intercellular Adhesion Molecule-1, -2, -3 Plasma Levels and Disease Activity of Ankylosing Spondylitis in the Chinese Han Population.

    PubMed

    Liu, Ruyin; Yue, Zongjin; Peng, Xiaoyan; Wang, Xinli; Feng, Zhongkai; Wan, Long

    2016-05-01

    We investigated the association between ICAM-1, -2, -3 plasma levels and ankylosing spondylitis (AS) disease activity. In the present study, we aimed to investigate the association between ICAM-1, -2, -3 plasma levels and AS disease activity in the Chinese Han population. AS is a chronic inflammatory rheumatic disease that effects the sacroiliac joints and axial skeleton. The intercellular adhesion molecules (ICAMs) are members of the immunoglobulin superfamily and have been identified to play major roles in inflammation and immune responses. A total of 60 patients with AS and 60 healthy individuals were selected. The plasma levels of proinflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and ICAM-1, -2, -3, were analyzed by ELISA. Disease severity-related indexes, including the Bath ankylosing spondylitis disease activity index (BASDAI), Bath ankylosing spondylitis functional index (BASFI), and ankylosing spondylitis disease activity score (ASDAS), were assessed, along with the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) level. Both ICAM-1 and ICAM-2 levels in plasma were markedly increased in AS patients compared with levels in the plasma of controls. There was no difference between controls and patients in term of ICAM-3 levels. Furthermore, in patients, correlation analysis showed that TNF-α and IL-6 production, as well as the ESR and CRP levels, have positive relationships with ICAM-1 and ICAM-2 plasma levels; the BASDAI, BASFI, and ASDAS scores were also found to be positively correlated with ICAM-2. However, no significant correlations between ICAM-1 levels and BASDAI, BASFI, or ASDAS were detected in our study. The current findings suggest that ICAM-2 may be a potential biomarker reflecting disease activity and functional ability in AS patients. 5.

  13. Circulating Concentrations of Monocyte Chemoattractant Protein-1, Plasminogen Activator Inhibitor-1, and Soluble Leukocyte Adhesion Molecule-1 in Overweight/Obese Men and Women Consuming Fructose- or Glucose-Sweetened Beverages for 10 Weeks

    PubMed Central

    Cox, Chad L.; Stanhope, Kimber L.; Schwarz, Jean Marc; Graham, James L.; Hatcher, Bonnie; Griffen, Steven C.; Bremer, Andrew A.; Berglund, Lars; McGahan, John P.; Keim, Nancy L.

    2011-01-01

    Context: Results from animal studies suggest that consumption of large amounts of fructose can promote inflammation and impair fibrinolysis. Data describing the effects of fructose consumption on circulating levels of proinflammatory and prothrombotic markers in humans are unavailable. Objective: Our objective was to determine the effects of 10 wk of dietary fructose or glucose consumption on plasma concentrations of monocyte chemoattractant protein-1 (MCP-1), plasminogen activator inhibitor-1 (PAI-1), E-selectin, intercellular adhesion molecule-1, C-reactive protein, and IL-6. Design and Setting: This was a parallel-arm study with two inpatient phases (2 wk baseline, final 2 wk intervention), conducted in a clinical research facility, and an outpatient phase (8 wk) during which subjects resided at home. Participants: Participants were older (40–72 yr), overweight/obese (body mass index = 25–35 kg/m2) men (n = 16) and women (n = 15). Interventions: Participants consumed glucose- or fructose-sweetened beverages providing 25% of energy requirements for 10 wk. Blood samples were collected at baseline and during the 10th week of intervention. Main Outcome Measures: Fasting concentrations of MCP-1 (P = 0.009), PAI-1 (P = 0.002), and E-selectin (P = 0.048) as well as postprandial concentrations of PAI-1 (P < 0.0001) increased in subjects consuming fructose but not in those consuming glucose. Fasting levels of C-reactive protein, IL-6, and intercellular adhesion molecule-1 were not changed in either group. Conclusions: Consumption of fructose for 10 wk leads to increases of MCP-1, PAI-1, and E-selectin. These findings suggest the possibility that fructose may contribute to the development of the metabolic syndrome via effects on proinflammatory and prothrombotic mediators. PMID:21956423

  14. Vascular cell adhesion molecule-1 (VCAM-1) plays a central role in the pathogenesis of severe forms of vasculitis due to hepatitis C-associated mixed cryoglobulinemia.

    PubMed

    Kaplanski, Gilles; Maisonobe, Thierry; Marin, Valérie; Grès, Sandra; Robitail, Stéphane; Farnarier, Catherine; Harlé, Jean-Robert; Piette, Jean-Charles; Cacoub, Patrice

    2005-03-01

    To better characterize the molecules involved in leukocyte tissue infiltration during hepatitis C-mixed cryoglobulinemia (HCV-MC)-associated vasculitis. The involvement of ELAM, ICAM-1 and VCAM-1 was evaluated in 36 patients with HCV-MC vasculitis using three different approaches: concentrations of soluble forms by specific ELISA, tissue expression by immunohistochemistry on patients nerve biopsies, endothelial expression by FACS analysis, on cells activated in vitro by cryoprecipitates purified from HCV-MC patients. Concentrations of sVCAM-1 were significantly elevated in the serum of HCV-MC patients compared to HCV patients without MC, the highest concentrations being found in severe vasculitis. VCAM-1 expression was detected on blood vessels from nerve biopsies performed in patients with severe vasculitis. When added to endothelial cells in vitro, HCV-MC patients cryoprecipitate induced VCAM-1 but also ELAM and ICAM-1 expression possibly through a mechanism due to the C1q complement fraction interaction with endothelial cells, since C1q was consistently present in the cryoprecipitates. VCAM-1 is mainly involved in the pathogenesis of HCV-MC-associated severe vasculitis and may be a potential interesting therapeutic target.

  15. Microarray expression profiling in adhesion and normal peritoneal tissues.

    PubMed

    Ambler, Dana R; Golden, Alicia M; Gell, Jennifer S; Saed, Ghassan M; Carey, David J; Diamond, Michael P

    2012-05-01

    To identify molecular markers associated with adhesion and normal peritoneal tissue using microarray expression profiling. Comparative study. University hospital. Five premenopausal women. Adhesion and normal peritoneal tissue samples were obtained from premenopausal women. Ribonucleic acid was extracted using standard protocols and processed for hybridization to Affymetrix Whole Transcript Human Gene Expression Chips. Microarray data were obtained from five different patients, each with adhesion tissue and normal peritoneal samples. Real-time polymerase chain reaction was performed for confirmation using standard protocols. Gene expression in postoperative adhesion and normal peritoneal tissues. A total of 1,263 genes were differentially expressed between adhesion and normal tissues. One hundred seventy-three genes were found to be up-regulated and 56 genes were down-regulated in the adhesion tissues compared with normal peritoneal tissues. The genes were sorted into functional categories according to Gene Ontology annotations. Twenty-six up-regulated genes and 11 down-regulated genes were identified with functions potentially relevant to the pathophysiology of postoperative adhesions. We evaluated and confirmed expression of 12 of these specific genes via polymerase chain reaction. The pathogenesis, natural history, and optimal treatment of postoperative adhesive disease remains unanswered. Microarray analysis of adhesions identified specific genes with increased and decreased expression when compared with normal peritoneum. Knowledge of these genes and ontologic pathways with altered expression provide targets for new therapies to treat patients who have or are at risk for postoperative adhesions. Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  16. Functional Mineralocorticoid Receptors in Human Vascular Endothelial Cells Regulate ICAM-1 Expression and Promote Leukocyte Adhesion

    PubMed Central

    Caprio, Massimiliano; Newfell, Brenna G.; la Sala, Andrea; Baur, Wendy; Fabbri, Andrea; Rosano, Giuseppe; Mendelsohn, Michael E.; Jaffe, Iris Z.

    2008-01-01

    In clinical trials, aldosterone antagonists decrease cardiovascular mortality and ischemia by unknown mechanisms. The steroid hormone aldosterone acts by binding to the mineralocorticoid receptor (MR), a ligand-activated transcription factor. In humans, aldosterone causes MR-dependent endothelial cell (EC) dysfunction and in animal models, aldosterone increases vascular macrophage infiltration and atherosclerosis. MR antagonists inhibit these effects without changing blood pressure, suggesting a direct role for vascular MR in EC function and atherosclerosis. Whether human vascular EC express functional MR is not known. Here we show that human coronary artery and aortic EC express MR mRNA and protein and that EC MR mediates aldosterone-dependent gene transcription. Human EC also express the enzyme 11-beta hydroxysteroid dehydrogenase-2(11βHSD2) and inhibition of 11βHSD2 in aortic EC enhances gene transactivation by cortisol, supporting that EC 11βHSD2 is functional. Furthermore, aldosterone stimulates transcription of the proatherogenic leukocyte-EC adhesion molecule Intercellular Adhesion Molecule-1(ICAM1) gene and protein expression on human coronary artery EC, an effect inhibited by the MR antagonist spironolactone and by MR knock-down with siRNA. Cell adhesion assays demonstrate that aldosterone promotes leukocyte-EC adhesion, an effect that is inhibited by spironolactone and ICAM1 blocking antibody, supporting that aldosterone induction of EC ICAM1 surface expression via MR mediates leukocyte-EC adhesion. These data show that aldosterone activates endogenous EC MR and proatherogenic gene expression in clinically important human EC. These studies describe a novel mechanism by which aldosterone may influence ischemic cardiovascular events and support a new explanation for the decrease in ischemic events in patients treated with aldosterone antagonists. PMID:18467630

  17. Application of negative ion MS/MS to the identification of N-glycans released from carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1).

    PubMed

    Harvey, David J; Baruah, Kavitha; Scanlan, Christopher N

    2009-01-01

    Structures of N-glycans released from rat CEACAM1 expressed in human embryonic kidney cells were determined by MALDI and negative ion nanospray MS/MS techniques. The major carbohydrates were bi-, tri- and tetra-antennary complex glycans with and without sialic acid, fucose and bisecting GlcNAc residues. High-mannose glycans, predominantly Man(5)GlcNAc(2), were also found. The negative ion fragmentation technique easily identified the branching pattern of the triantennary glycans (mainly branched on the 6-antenna) and the presence of 'bisecting' GlcNAc residues (attached to the 4-position of the core mannose), features that are difficult to determine by traditional techniques. Sialic acids were in both alpha2-3 and alpha2-6 linkage as determined by MALDI-TOF MS following linkage-specific derivatization. (c) 2008 John Wiley & Sons, Ltd.

  18. Tenomodulin Expression in the Periodontal Ligament Enhances Cellular Adhesion

    PubMed Central

    Komiyama, Yuske; Ohba, Shinsuke; Shimohata, Nobuyuki; Nakajima, Keiji; Hojo, Hironori; Yano, Fumiko; Takato, Tsuyoshi; Docheva, Denitsa; Shukunami, Chisa; Hiraki, Yuji; Chung, Ung-il

    2013-01-01

    Tenomodulin (Tnmd) is a type II transmembrane protein characteristically expressed in dense connective tissues such as tendons and ligaments. Its expression in the periodontal ligament (PDL) has also been demonstrated, though the timing and function remain unclear. We investigated the expression of Tnmd during murine tooth eruption and explored its biological functions in vitro. Tnmd expression was related to the time of eruption when occlusal force was transferred to the teeth and surrounding tissues. Tnmd overexpression enhanced cell adhesion in NIH3T3 and human PDL cells. In addition, Tnmd-knockout fibroblasts showed decreased cell adhesion. In the extracellular portions of Tnmd, the BRICHOS domain or CS region was found to be responsible for Tnmd-mediated enhancement of cell adhesion. These results suggest that Tnmd acts on the maturation or maintenance of the PDL by positively regulating cell adhesion via its BRICHOS domain. PMID:23593173

  19. Carbamylated low-density lipoprotein induces proliferation and increases adhesion molecule expression of human coronary artery smooth muscle cells.

    PubMed

    Asci, Gulay; Basci, Ali; Shah, Sudhir V; Basnakian, Alexei; Toz, Huseyin; Ozkahya, Mehmet; Duman, Soner; Ok, Ercan

    2008-12-01

    Presence of accelerated atherosclerosis in dialysis patients cannot be entirely explained by conventional risk factors. Exposure to urea, which is elevated in patients with kidney disease, leads to the carbamylation of proteins. We investigated the effects of carbamylated low-density lipoprotein (cLDL) on human coronary artery vascular smooth muscle cells (VSMC). Native LDL (nLDL) was carbamylated with potassium cyanate. Cells were incubated with different concentrations of cLDL carbamylated at different time points. Cytotoxicity, apoptosis, proliferation (bromodeoxyuridine incorporation), expression of adhesion molecules and extracellular matrix protein synthesis were studied. Carbamylated low-density lipoprotein exposure leads to morphological alterations and presence of cellular debris. Neither nLDL nor cLDL caused apoptosis. Lactate dehydrogenase (LDH) release was not different between groups. Carbamylated low-density lipoprotein led to a striking proliferation in VSMC compared to nLDL. Carbamylated low-density lipoprotein significantly increased intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 expression compared to the control. The effects of cLDL on proliferation and adhesion molecule expression were dose-dependent and correlated with the degree of low-density lipoprotein carbamylation. cLDL had no effect on extracellular matrix protein synthesis. The results support the hypothesis that cLDL may contribute to the pathogenesis of atherosclerosis in uraemic patients.

  20. Oncostatin M is a proinflammatory mediator. In vivo effects correlate with endothelial cell expression of inflammatory cytokines and adhesion molecules.

    PubMed Central

    Modur, V; Feldhaus, M J; Weyrich, A S; Jicha, D L; Prescott, S M; Zimmerman, G A; McIntyre, T M

    1997-01-01

    Oncostatin M is a member of the IL-6 family of cytokines that is primarily known for its effects on cell growth. Endothelial cells have an abundance of receptors for oncostatin M, and may be its primary target. We determined if oncostatin M induces a key endothelial cell function, initiation of the inflammatory response. We found that subcutaneous injection of oncostatin M in mice caused an acute inflammatory reaction. Oncostatin M in vitro stimulated: (a) polymorphonuclear leukocyte (PMN) transmigration through confluent monolayers of primary human endothelial cells; (b) biphasic PMN adhesion through rapid P-selectin expression, and delayed adhesion mediated by E-selectin synthesis; (c) intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 accumulation; and (d) the expression of PMN activators IL-6, epithelial neutrophil activating peptide-78, growth-related cytokine alpha and growth-related cytokine beta without concomitant IL-8 synthesis. The nature of the response to oncostatin M varied with concentration, suggesting high and low affinity oncostatin M receptors independently stimulated specific responses. Immunohistochemistry showed that macrophage-like cells infiltrating human aortic aneurysms expressed oncostatin M, so it is present during a chronic inflammatory reaction. Therefore, oncostatin M, but not other IL-6 family members, fulfills Koch's postulates as an inflammatory mediator. Since its effects on endothelial cells differ significantly from established mediators like TNFalpha, it may uniquely contribute to the inflammatory cycle. PMID:9202068

  1. Omentin inhibits TNF-α-induced expression of adhesion molecules in endothelial cells via ERK/NF-κB pathway.

    PubMed

    Zhong, Xia; Li, Xiaonan; Liu, Fuli; Tan, Hui; Shang, Deya

    2012-08-24

    In the present study, we investigated whether omentin affected the expression of intracellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in tumor necrosis factor-α (TNF-α) induced human umbilical vein endothelial cells (HUVECs). Our data showed that omentin decreased TNF-α-induced expression of ICAM-1 and VCAM-1 in HUVECs. In addition, omentin inhibited TNF-α-induced adhesion of THP-1 cells to HUVECs. Further, we found that omentin inhibited TNF-α-activated signal pathway of nuclear factor-κB (NF-κB) by preventing NF-κB inhibitory protein (IκBα) degradation and NF-κB/DNA binding activity. Omentin pretreatment significantly inhibited TNF-α-induced ERK activity and ERK phosphorylation in HUVECs. Pretreatment with PD98059 suppressed TNF-α-induced NF-κB activity. Omentin, NF-kB inhibitor (BAY11-7082) and ERK inhibitor (PD98059) reduced the up-regulation of ICAM-1 and VCAM-1 induced by TNF-α. These results suggest that omentin may inhibit TNF-α-induced expression of adhesion molecules in endothelial cells via blocking ERK/NF-κB pathway.

  2. Erythromycin exerts in vivo anti-inflammatory activity downregulating cell adhesion molecule expression

    PubMed Central

    Sanz, María-Jesús; Nabah, Yafa Naim Abu; Cerdá-Nicolás, Miguel; O'Connor, José-Enrique; Issekutz, Andrew C; Cortijo, Julio; Morcillo, Esteban J

    2004-01-01

    Macrolides have long been used as anti-bacterial agents; however, there is some evidence that may exert anti-inflammatory activity. Therefore, erythromycin was used to characterize the mechanisms involved in their in vivo anti-inflammatory activity. Erythromycin pretreatment (30 mg kg−1 day−1 for 1 week) reduced the lipopolysaccharide (LPS; intratracheal, 0.4 mg kg−1)-induced increase in neutrophil count and elastase activity in the bronchoalveolar lavage fluid (BALF) and lung tissue myeloperoxidase activity, but failed to decrease tumor necrosis factor-α and macrophage-inflammatory protein-2 augmented levels in BALF. Erythromycin pretreatment also prevented lung P-selectin, E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) mRNA upregulation in response to airway challenge with LPS. Mesentery superfusion with LPS (1 μg ml−1) induced a significant increase in leukocyte–endothelial cell interactions at 60 min. Erythromycin pretreatment abolished the increases in these parameters. LPS exposure of the mesentery for 4 h caused a significant increase in leukocyte rolling flux, adhesion and emigration, which were inhibited by erythromycin by 100, 93 and 95%, respectively. Immunohistochemical analysis showed that LPS exposure of the mesentery for 4 h caused a significant enhancement in P-selectin, E-selectin, ICAM-1 and VCAM-1 expression that was downregulated by erythromycin pretreatment. Flow cytometry analysis indicated that erythromycin pretreatment inhibited LPS-induced CD11b augmented expression in rat neutrophils. In conclusion, erythromycin inhibits leukocyte recruitment in the lung and this effect appears mediated through downregulation of CAM expression. Therefore, macrolides may be useful in the control of neutrophilic pulmonary diseases. PMID:15665859

  3. ETA receptor mediates altered leukocyte-endothelial cell interaction and adhesion molecules expression in DOCA-salt rats.

    PubMed

    Callera, Glaucia E; Montezano, Augusto C; Touyz, Rhian M; Zorn, Telma M T; Carvalho, Maria Helena C; Fortes, Zuleica B; Nigro, Dorothy; Schiffrin, Ernesto L; Tostes, Rita C

    2004-04-01

    Leukocyte adhesion to endothelial cells plays a key role in inflammatory processes associated with end-organ injury. Endothelin-1 (ET-1), which stimulates inflammatory processes, contributes to cardiovascular damage in deoxycorticosterone (DOCA)-salt hypertension. We investigated whether ETA receptor blockade modulates in vivo leukocyte-endothelial cell interactions and expression of cell adhesion molecules (CAM) involved in these processes. DOCA-salt and control uninephrectomized rats were treated with the ETA antagonist BMS182874 (40 mg/kg per day) or vehicle. Analysis of CAMs expression by reverse transcription-polymerase chain reaction and immunohistochemistry showed increased cardiac platelet selectin (P-selectin), detected mainly in endothelial cells, and vascular cell adhesion molecule-1 (VCAM-1), but not intercellular adhesion molecule-1 (ICAM-1), in DOCA-salt rats. Cardiac expression of endothelial selectin (E-selectin) was decreased, whereas immunoreactivity to ED-1 and myeloperoxidase (MPO) activity, markers of macrophage and leukocyte infiltration, respectively, were increased in DOCA-salt. Leukocyte-endothelial cell interaction, functionally assessed in venules of internal spermatic fascia by intravital microscopy, was significantly altered in DOCA-salt rats as evidenced by increased leukocyte adhesion and decreased rolling. BMS182874 treatment normalized leukocyte-endothelium interactions, decreased cardiac VCAM-1 expression in DOCA and control groups, and had no effects on ICAM-1 expression. BMS182874 also increased E-selectin and abolished P-selectin expression in DOCA-salt, but not in control rats. The ETA antagonist reduced cardiac ED-1 content and MPO activity and prevented cardiac damage in DOCA-salt rats. These data indicate that ET-1 participates, via activation of ETA receptors, in altered leukocyte-endothelial cell interactions in DOCA-salt rats, possibly by modulating expression of CAMs, and that the inflammatory status is associated with

  4. Effects of plasma treated PET and PTFE on expression of adhesion molecules by human endothelial cells in vitro.

    PubMed

    Pu, F R; Williams, R L; Markkula, T K; Hunt, J A

    2002-06-01

    The aim of this study was to evaluate the expression of adhesion molecules on the surface of human endothelial cells in response to the systematic variation in materials properties by the ammonia plasma modification of polyethylene terephthalate (PET) and polytetrafluorethylene (PTFE). These adhesion molecules act as mediators of cell adhesion, play a role in the modulation of cell adhesion on biomaterials and therefore condition the response of tissues to implants. First and second passage human umbilical vein endothelial cells (HUVECs) were cultured on plasma treated and untreated PET and PTFE. HUVECs grown on polystyrene tissue culture coverslips and HUVECs stimulated with tumour necrosis factor (TNF-alpha) were used as controls. After 1 day and 7 days, the expression of adhesion molecules platelet endothelial cell adhesion molecule-1 (PECAM-1), intercellular adhesion molecule-1 (ICAM-1), Integrin alphavbeta3, vascular cell adhesion molecule-1 (VCAM-1), E-selectin, P-selectin and L-selectin were evaluated using flow cytometry and immunohistochemistry. There was a slight increase in positive cell numbers expressing the adhesion molecules ICAM-1 and VCAM-1 on plasma treated PET and PTFE. A significant increase in E-selectin positive cells on untreated PTFE was demonstrated after 7 days. Stimulation with TNF-alpha demonstrated a significant increase in the proportion of ICAM-1. VCAM-1 and E-selectin positive cells. Almost all cells expressed PECAM-1 and integrin alphavbeta3, on both materials and controls but did not express P- and L-selectin on any surface. When second passage cells were used, the expression of the adhesion molecules ICAM-1 and VCAM-1 was markedly increased on all surfaces but not with TNF-alpha. These significant differences were not observed in other adhesion molecules. These results were supported by immunohistochemical studies. The effects of plasma treated PET and PTFE on cell adhesion and proliferation was also studied. There was a 1.3-fold

  5. Epstein-Barr Virus–induced Molecule 1 Ligand Chemokine Is Expressed by Dendritic Cells in Lymphoid Tissues and Strongly Attracts Naive T Cells and Activated B Cells

    PubMed Central

    Ngo, Vu N.; Lucy Tang, H.; Cyster, Jason G.

    1998-01-01

    Movement of T and B lymphocytes through secondary lymphoid tissues is likely to involve multiple cues that help the cells navigate to appropriate compartments. Epstein-Barr virus– induced molecule 1 (EBI-1) ligand chemokine (ELC/MIP3β) is expressed constitutively within lymphoid tissues and may act as such a guidance cue. Here, we have isolated mouse ELC and characterized its expression pattern and chemotactic properties. ELC is expressed constitutively in dendritic cells within the T cell zone of secondary lymphoid tissues. Recombinant ELC was strongly chemotactic for naive (L-selectinhi) CD4 T cells and for CD8 T cells and weakly attractive for resting B cells and memory (L-selectinlo) CD4 T cells. After activation through the B cell receptor, the chemotactic response of B cells was enhanced. Like its human counterpart, murine ELC stimulated cells transfected with EBI-1/CC chemokine receptor 7 (CCR7). Our findings suggest a central role for ELC in promoting encounters between recirculating T cells and dendritic cells and in the migration of activated B cells into the T zone of secondary lymphoid tissues. PMID:9653094

  6. Epstein-Barr virus-induced molecule 1 ligand chemokine is expressed by dendritic cells in lymphoid tissues and strongly attracts naive T cells and activated B cells.

    PubMed

    Ngo, V N; Tang, H L; Cyster, J G

    1998-07-06

    Movement of T and B lymphocytes through secondary lymphoid tissues is likely to involve multiple cues that help the cells navigate to appropriate compartments. Epstein-Barr virus- induced molecule 1 (EBI-1) ligand chemokine (ELC/MIP3beta) is expressed constitutively within lymphoid tissues and may act as such a guidance cue. Here, we have isolated mouse ELC and characterized its expression pattern and chemotactic properties. ELC is expressed constitutively in dendritic cells within the T cell zone of secondary lymphoid tissues. Recombinant ELC was strongly chemotactic for naive (L-selectinhi) CD4 T cells and for CD8 T cells and weakly attractive for resting B cells and memory (L-selectinlo) CD4 T cells. After activation through the B cell receptor, the chemotactic response of B cells was enhanced. Like its human counterpart, murine ELC stimulated cells transfected with EBI-1/CC chemokine receptor 7 (CCR7). Our findings suggest a central role for ELC in promoting encounters between recirculating T cells and dendritic cells and in the migration of activated B cells into the T zone of secondary lymphoid tissues.

  7. Expression of adhesion molecules, chemokines and matrix metallo- proteinases (MMPs) in viable and degenerating stage of Taenia solium metacestode in swine neurocysticercosis.

    PubMed

    Singh, Satyendra K; Singh, Aloukick K; Prasad, Kashi N; Singh, Amrita; Singh, Avinash; Rai, Ravi P; Tripathi, Mukesh; Gupta, Rakesh K; Husain, Nuzhat

    2015-11-30

    Neurocysticercosis (NCC) is a parasitic infection of central nervous system (CNS). Expression of adhesion molecules, chemokines and matrix metalloproteinases (MMPs) were investigated on brain tissues surrounding viable (n=15) and degenerating cysticerci (n=15) of Taenia solium in swine by real-time RT-PCR and ELISA. Gelatin gel zymography was performed for MMPs activity. ICAM-1 (intercellular adhesion molecule-1), E-selectin, MIP-1α (macrophage inflammatory protein-1α), Eotaxin-1 and RANTES (regulated on activation, normal T cell expressed and secreted) were associated with degenerating cysticerci (cysts). However, VCAM-1 (vascular cell adhesion molecule-1), MCP-1 (monocyte chemotactic protein-1), MMP-2 and MMP-9 were associated with both viable and degenerating cysts. In conclusion, viable and degenerating cysticerci have different immune molecule profiles and role of these molecules in disease pathogenesis needs to be investigated.

  8. Human immunodeficiency virus type 1 induces cellular polarization, intercellular adhesion molecule-1 redistribution, and multinucleated giant cell generation in human primary monocytes but not in monocyte-derived macrophages.

    PubMed

    Fais, S; Borghi, P; Gherardi, G; Logozzi, M; Belardelli, F; Gessani, S

    1996-12-01

    In this study, we evaluated the effects of human immunodeficiency virus type 1 (HIV-1) on some morphologic and functional changes in cultured human monocytes/macrophages at different stages of differentiation. Freshly isolated monocytes infected with HIV-1 24 hours after seeding exhibited marked morphologic changes such as uropod formation, polarization of intercellular adhesion molecule-1 (ICAM-1) on the cytoplasmic projection, the redistribution of alpha-actinin on cell-membrane dots, and an increased release of soluble ICAM-1. These changes preceded the increase in monocyte-monocyte fusion and the formation of multinucleated giant cells. In contrast, HIV-1 infection did not affect monocyte-derived macrophages in terms of either cellular polarization or multinucleated giant cell formation. Immunocytochemistry showed that HIV-1 matrix protein was present mostly in bi- and trinucleated cells, which suggests that multinucleated giant cells may represent a long-lived and highly productive cellular source of HIV. The treatment of the HIV-1-infected monocytes with azidodeoxythymidine virtually abolished all viral-induced morphofunctional changes. On the whole, these results indicate that blood monocytes and differentiated macrophages may be affected differently by HIV infection, as monocytes seem to be much more prone to polarize, undergo homotypic fusion, and form multinucleated giant cells. These changes may confer to HIV-infected monocytes an increased ability to transmigrate through endothelia into tissues, whereas differentiated macrophages may have a predominant role as a widespread reservoir of HIV.

  9. A single-arm, open-label, phase 2 clinical trial evaluating disease response following treatment with BI-505, a human anti-intercellular adhesion molecule-1 monoclonal antibody, in patients with smoldering multiple myeloma

    PubMed Central

    Wichert, Stina; Juliusson, Gunnar; Johansson, Åsa; Sonesson, Elisabeth; Teige, Ingrid; Wickenberg, Anna Teige; Frendeus, Björn; Korsgren, Magnus; Hansson, Markus

    2017-01-01

    Background Smoldering multiple myeloma (SMM) is an indolent disease stage, considered to represent the transition phase from the premalignant MGUS (Monoclonal Gammopathy of Undetermined Significance) state towards symptomatic multiple myeloma (MM). Even though this diagnosis provides an opportunity for early intervention, few treatment studies have been done and the current standard of care is observation until progression. BI-505, a monoclonal antibody directed against intercellular adhesion molecule 1 (ICAM-1) with promising anti-myeloma activity in preclinical trials, is a possible treatment approach for this patient category with potential to eliminate tumor cells with minimal long-term side effects. BI-505 was well tolerated in an earlier phase 1 trial. Methods and findings In this phase 2 trial the effects of BI-505 in patients with SMM were studied. Four patients were enrolled and three of them completed the first cycle of treatment defined as 5 doses of BI-505, a total of 43 mg/kg BW, over a 7-week period. In the three evaluable patients, BI-505 showed a benign safety profile. None of the patients achieved a response as defined per protocol. EudraCT number: 2012-004884-29. Conclusions The study was conducted to assess the efficacy, safety and pharmacodynamics of BI-505 in patients with SMM. BI-505 showed no clinically relevant efficacy on disease activity in these patients with SMM, even if well tolerated. Trial registration ClinicalTrials.gov Identifier: NCT01838369. PMID:28158311

  10. A single-arm, open-label, phase 2 clinical trial evaluating disease response following treatment with BI-505, a human anti-intercellular adhesion molecule-1 monoclonal antibody, in patients with smoldering multiple myeloma.

    PubMed

    Wichert, Stina; Juliusson, Gunnar; Johansson, Åsa; Sonesson, Elisabeth; Teige, Ingrid; Wickenberg, Anna Teige; Frendeus, Björn; Korsgren, Magnus; Hansson, Markus

    2017-01-01

    Smoldering multiple myeloma (SMM) is an indolent disease stage, considered to represent the transition phase from the premalignant MGUS (Monoclonal Gammopathy of Undetermined Significance) state towards symptomatic multiple myeloma (MM). Even though this diagnosis provides an opportunity for early intervention, few treatment studies have been done and the current standard of care is observation until progression. BI-505, a monoclonal antibody directed against intercellular adhesion molecule 1 (ICAM-1) with promising anti-myeloma activity in preclinical trials, is a possible treatment approach for this patient category with potential to eliminate tumor cells with minimal long-term side effects. BI-505 was well tolerated in an earlier phase 1 trial. In this phase 2 trial the effects of BI-505 in patients with SMM were studied. Four patients were enrolled and three of them completed the first cycle of treatment defined as 5 doses of BI-505, a total of 43 mg/kg BW, over a 7-week period. In the three evaluable patients, BI-505 showed a benign safety profile. None of the patients achieved a response as defined per protocol. EudraCT number: 2012-004884-29. The study was conducted to assess the efficacy, safety and pharmacodynamics of BI-505 in patients with SMM. BI-505 showed no clinically relevant efficacy on disease activity in these patients with SMM, even if well tolerated. ClinicalTrials.gov Identifier: NCT01838369.

  11. Hyperketonemia increases monocyte adhesion to endothelial cells and is mediated by LFA-1 expression in monocytes and ICAM-1 expression in endothelial cells

    PubMed Central

    Rains, Justin L.

    2011-01-01

    Frequent episodes of hyperketonemia are associated with a higher incidence of vascular disease. The objective of this study was to examine the hypothesis that hyperketonemia increases monocyte-endothelial cell (EC) adhesion and the development of vascular disease in diabetes. Human U937 and THP-1 monocyte cell lines and human umbilical vein endothelial cells (HUVECs) were cultured with acetoacetate (AA) (0–10 mM) or β-hydroxybutyrate (BHB) (0–10 mM) for 24 h prior to evaluating adhesion and adhesion molecule expression. The results demonstrate a significant (P < 0.01) increase in both U937 and THP-1 adhesion to HUVEC monolayers treated with 4 mM AA compared with control. Equal concentrations of BHB resulted in similar increases in monocyte-EC adhesion. Similarly, treatments of AA or BHB to isolated monocytes from human blood also show increases in adhesion to endothelial cells. intercellular adhesion molecule-1 (ICAM-1) was significantly increased on the surface of HUVECs and an increase in total protein expression with AA treatment compared with control. The expression level of lymphocyte function-associated antigen-1 (LFA-1) was increased in monocytes treated with AA, and LFA-1 affinity was altered from low to high affinity following treatment with both AA and BHB. Monocyte adhesion could be blocked when cells were preincubated with an antibody to ICAM-1 or LFA-1. Results also show a significant increase in IL-8 and MCP-1 secretion in monocytes and HUVECs treated with 0–10 mM AA. These results suggest that hyperketonemia can induce monocyte adhesion to endothelial cells and that it is mediated via increased ICAM-1 expression in endothelial cells and increased expression and affinity of LFA-1 in monocytes. PMID:21540444

  12. Hyperketonemia increases monocyte adhesion to endothelial cells and is mediated by LFA-1 expression in monocytes and ICAM-1 expression in endothelial cells.

    PubMed

    Rains, Justin L; Jain, Sushil K

    2011-08-01

    Frequent episodes of hyperketonemia are associated with a higher incidence of vascular disease. The objective of this study was to examine the hypothesis that hyperketonemia increases monocyte-endothelial cell (EC) adhesion and the development of vascular disease in diabetes. Human U937 and THP-1 monocyte cell lines and human umbilical vein endothelial cells (HUVECs) were cultured with acetoacetate (AA) (0-10 mM) or β-hydroxybutyrate (BHB) (0-10 mM) for 24 h prior to evaluating adhesion and adhesion molecule expression. The results demonstrate a significant (P < 0.01) increase in both U937 and THP-1 adhesion to HUVEC monolayers treated with 4 mM AA compared with control. Equal concentrations of BHB resulted in similar increases in monocyte-EC adhesion. Similarly, treatments of AA or BHB to isolated monocytes from human blood also show increases in adhesion to endothelial cells. intercellular adhesion molecule-1 (ICAM-1) was significantly increased on the surface of HUVECs and an increase in total protein expression with AA treatment compared with control. The expression level of lymphocyte function-associated antigen-1 (LFA-1) was increased in monocytes treated with AA, and LFA-1 affinity was altered from low to high affinity following treatment with both AA and BHB. Monocyte adhesion could be blocked when cells were preincubated with an antibody to ICAM-1 or LFA-1. Results also show a significant increase in IL-8 and MCP-1 secretion in monocytes and HUVECs treated with 0-10 mM AA. These results suggest that hyperketonemia can induce monocyte adhesion to endothelial cells and that it is mediated via increased ICAM-1 expression in endothelial cells and increased expression and affinity of LFA-1 in monocytes.

  13. Microglia of medicinal leech (Hirudo medicinalis) express a specific activation marker homologous to vertebrate ionized calcium-binding adapter molecule 1 (Iba1/alias aif-1).

    PubMed

    Drago, Francesco; Sautière, Pierre-Eric; Le Marrec-Croq, Françoise; Accorsi, Alice; Van Camp, Christelle; Salzet, Michel; Lefebvre, Christophe; Vizioli, Jacopo

    2014-10-01

    The Ionized calcium-Binding Adapter molecule 1 (Iba1), also known as Allograft Inflammatory Factor 1 (AIF-1), is a 17 kDa cytokine-inducible protein, produced by activated macrophages during chronic transplant rejection and inflammatory reactions in Vertebrates. In mammalian central nervous system (CNS), Iba1 is a sensitive marker associated with activated macrophages/microglia and is upregulated following neuronal death or brain lesions. The medicinal leech Hirudo medicinalis is able to regenerate its CNS after injury, leading to a complete functional repair. Similar to Vertebrates, leech neuroinflammatory processes are linked to microglia activation and recruitment at the lesion site. We identified a gene, named Hmiba1, coding a 17.8 kDa protein showing high similarity with Vertebrate AIF-1. The present work constitutes the first report on an Iba1 protein in the nervous system of an invertebrate. Immunochemistry and gene expression analyses showed that HmIba1, like its mammalian counterpart, is modulated in leech CNS by mechanical injury or chemical stimuli (ATP). We presently demonstrate that most of leech microglial cells migrating and accumulating at the lesion site specifically expressed the activation marker HmIba1. While the functional role of Iba1, whatever species, is still unclear in reactive microglia, this molecule appeared as a good selective marker of activated cells in leech and presents an interesting tool to investigate the functions of these cells during nerve repair events. © 2014 Wiley Periodicals, Inc.

  14. Omentin inhibits TNF-{alpha}-induced expression of adhesion molecules in endothelial cells via ERK/NF-{kappa}B pathway

    SciTech Connect

    Zhong, Xia; Li, Xiaonan; Liu, Fuli; Tan, Hui; Shang, Deya

    2012-08-24

    Highlights: Black-Right-Pointing-Pointer Omentin inhibited TNF-{alpha}-induced adhesion of THP-1 cells to HUVECs. Black-Right-Pointing-Pointer Omentin reduces expression of ICAM-1 and VCAM-1 induced by TNF-{alpha} in HUVECs. Black-Right-Pointing-Pointer Omentin inhibits TNF-{alpha}-induced ERK and NF-{kappa}B activation in HUVECs. Black-Right-Pointing-Pointer Omentin supreeses TNF-{alpha}-induced expression of ICAM-1 and VCAM-1 via ERK/NF-{kappa}B pathway. -- Abstract: In the present study, we investigated whether omentin affected the expression of intracellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in tumor necrosis factor-{alpha} (TNF-{alpha}) induced human umbilical vein endothelial cells (HUVECs). Our data showed that omentin decreased TNF-{alpha}-induced expression of ICAM-1 and VCAM-1 in HUVECs. In addition, omentin inhibited TNF-{alpha}-induced adhesion of THP-1 cells to HUVECs. Further, we found that omentin inhibited TNF-{alpha}-activated signal pathway of nuclear factor-{kappa}B (NF-{kappa}B) by preventing NF-{kappa}B inhibitory protein (I{kappa}B{alpha}) degradation and NF-{kappa}B/DNA binding activity. Omentin pretreatment significantly inhibited TNF-{alpha}-induced ERK activity and ERK phosphorylation in HUVECs. Pretreatment with PD98059 suppressed TNF-{alpha}-induced NF-{kappa}B activity. Omentin, NF-kB inhibitor (BAY11-7082) and ERK inhibitor (PD98059) reduced the up-regulation of ICAM-1 and VCAM-1 induced by TNF-{alpha}. These results suggest that omentin may inhibit TNF-{alpha}-induced expression of adhesion molecules in endothelial cells via blocking ERK/NF-{kappa}B pathway.

  15. Expression, crystallization and preliminary X-ray diffraction analysis of the CMM2 region of the Arabidopsis thaliana Morpheus' molecule 1 protein.

    PubMed

    Petty, Tom J; Nishimura, Taisuke; Emamzadah, Soheila; Gabus, Caroline; Paszkowski, Jerzy; Halazonetis, Thanos D; Thore, Stéphane

    2010-08-01

    Of the known epigenetic control regulators found in plants, the Morpheus' molecule 1 (MOM1) protein is atypical in that the deletion of MOM1 does not affect the level of epigenetic marks controlling the transcriptional status of the genome. A short 197-amino-acid fragment of the MOM1 protein sequence can complement MOM1 deletion when coupled to a nuclear localization signal, suggesting that this region contains a functional domain that compensates for the loss of the full-length protein. Numerous constructs centred on the highly conserved MOM1 motif 2 (CMM2) present in these 197 residues have been generated and expressed in Escherichia coli. Following purification and crystallization screening, diamond-shaped single crystals were obtained that diffracted to approximately 3.2 A resolution. They belonged to the trigonal space group P3(1)21 (or P3(2)21), with unit-cell parameters a=85.64, c=292.74 A. Structure determination is ongoing.

  16. Expression of inducible cell adhesion molecules in the normal human lung: immunohistochemical study of their distribution in pulmonary blood vessels.

    PubMed

    Feuerhake, F; Füchsl, G; Bals, R; Welsch, U

    1998-10-01

    The distribution of cell adhesion molecules in the normal human lung was investigated using antibodies to E-selectin, P-selectin, intercellular adhesion molecule 1(ICAM-1), and vascular cell adhesion molecule 1 (VCAM-1). Lectin staining by Ulex europaeus type I agglutinin (UEA I) and immunohistochemistry for von Willebrand factor (vWF) was used to visualize a maximum of blood vessels per section. In the bronchial mucosa, staining for P-selectin was positive in ca 90%, and staining for E-selectin, VCAM-1, and ICAM-1 was positive in 40-70% of the vessels stained with UEA I. In the pulmonary circulation (vasa publica) ca 90% of non-capillary vessels stained by anti-vWF expressed P-selectin, 54% VCAM-1, 41% E-selectin, and only ca 20% ICAM 1. The alveolar capillaries were stained consistently by UEA I, but not by the panel of antibodies tested. The alveolar epithelium and, inconstantly, basal cells of the bronchial epithelium were positive for ICAM-1. The distribution pattern of inducible adhesion molecules in normal human lung tissue suggests that a permanent low-grade endothelial activation may exist in particular in the mucosa of the airways, which could be due to the normal antigen exposure via inhaled air.

  17. Dealcoholised beers reduce atherosclerosis and expression of adhesion molecules in apoE-deficient mice.

    PubMed

    Martinez, Nuria; Urpi-Sarda, Mireia; Martinez-Gonzalez, Miguel Angel; Andres-Lacueva, Cristina; Mitjavila, Maria Teresa

    2011-03-01

    Polyphenols exert beneficial effects in atherosclerosis. The crucial step in atherosclerosis is the recruitment of monocytes to the subendothelial space, induced by endothelial adhesion molecules through the activation of factors such as NF-κB. We studied the effect of a dealcoholised lager beer (DLB) and a dealcoholised dark beer (DDB) on atherosclerotic lesions, and the underlying mechanisms. Dealcoholised beers were administered in the diet (42 ml/kg body weight per d) to 4-week-old male apoE knockout (apoE - / - ) mice for 20 weeks. The atherosclerotic lesions in the thoracic aorta were reduced by 44 % (P = 0·003) and 51 % (P < 0·001) in DLB- and DDB-treated mice, respectively. Also, the mRNA expressions of the endothelial adhesion molecules in the total aorta were decreased: P-selectin showed a 17 % (P = 0·004) reduction in DDB-treated mice; vascular cell adhesion molecule-1 (VCAM-1) was decreased by 20 % (P = 0·012) and 32 % (P = 0·001) in DLB- and DDB-treated mice, respectively; intercellular adhesion molecule-1 (ICAM-1) showed a 14 % (P = 0·014) reduction in DLB-treated mice. The protein expressions of these molecules and NF-κB were studied in the aortic root. P-selectin was decreased by 37 % (P = 0·012) in DDB-treated mice; VCAM-1 was reduced by 48 % (P = 0·001) and 54 % (P < 0·001) in DLB- and DDB-treated mice, respectively; ICAM-1 was decreased by 25 % (P = 0·028) and 30 % (P = 0·018) in DLB- and DDB-treated mice, respectively; NF-κB was reduced by 46 % (P = 0·042) in DDB-treated mice. In conclusion, dealcoholised beers protected apoE - / -  mice against atherosclerosis, through the modulation of endothelial adhesion molecules, possibly induced by NF-κB.

  18. [Effect of non-surgical periodontal therapy on level of serum soluble intercellular adhesion molecule-1 and glycated hemoglobin A1c in patients with type 2 diabetes and chronic periodontitis].

    PubMed

    Yuan, Tangxia; Zhang, Yanbiao; Zhou, Yun; Wang, Fantao; Wang, Feng

    2013-08-01

    To evaluate the effects of non-surgical periodontal treatment on clinical periodontal measurements, glycemic control, and level of serum soluble intercellular adhesion molecule-1 (sICAM-1) in type 2 diabetes mellitus with chronic periodontitis patients. Patients with type 2 diabetes and chronic periodontitis were selected and classified into well-controlled group[glycated hemoglobin Ac(GHbA1)<7.00%, n=30, DMCP1 group] and poorly-controlled group (GHbAc > or = 7.00%, n = 30, DMCP2 group). Thirty systemically healthy patients with chronic periodontitis were recruited as control group (CP group). All subjects underwent non-surgical periodontal therapy. Plaque index(PLI), sulcus bleeding index(SBI), bleeding on probing (BOP), probing depth(PD), clinical attachment loss (CAL), serum sICAM-1 concentration, and the value of fasting plasma glucose(FPG), GHbAc were recorded at baseline, 1 and 3 months after periodontal treatment. The three study groups showed significant improvements for the levels of PD, SBI, PLI, BOP, and serum sICAM-1 concentration at 1 and 3 months after non-surgical periodontal treatment (P < 0.05). The level of CP group and DMCP1 group also showed significant improvements for the levels of CAL (P < 0.05), but no significant change was found in DMCP2 group (P > 0.05). At 3 months after periodontal treatment, GHbA1c levels in DMCP2 group significantly decreased by 1.12% (P < 0.05), whereas no significant changes were found in CP and DMCT groups (P > 0.05). Non-surgical periodontal treatment can siginificantly improve periodontal health status in patients with type 2 diabetes and periodontitis, reduce the level of serum sICAM-1, and can reduce the level of GHbA1c in poorly controlled type 2 diabetic patients.

  19. Neuroprotectant androst-3β, 5α, 6β-triol suppresses TNF-α-induced endothelial adhesion molecules expression and neutrophil adhesion to endothelial cells by attenuation of CYLD-NF-κB pathway.

    PubMed

    Yan, Min; Leng, Tiandong; Tang, Lipeng; Zheng, Xiaoke; Lu, Bingzheng; Li, Yuan; Sheng, Longxiang; Lin, Suizhen; Shi, Haitao; Yan, Guangmei; Yin, Wei

    2017-02-05

    Neuroinflammation is one of key pathologic element in neurological diseases including stroke, traumatic brain injury, Alzheimer' s Disease, Parkinson's Disease, and multiple sclerosis as well. Up-regulation of endothelial adhesion molecules, which facilitate leukocyte adhesion to the endothelium, is the vital process of endothelial cells mediated neuroinflammation. Androst-3β, 5α, 6β-triol (Triol) is a synthetic steroid which has been reported to have neuroprotective effects in hypoxia/re-oxygenation-induced neuronal injury model. In the present study, we firstly investigated whether Triol inhibited the TNF-α-induced inflammatory response in rat brain microvascular endothelial cells (RBMECs). Our data showed that Triol decreased TNF-α-induced expression of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) and the adhesion of neutrophil to RBMECs. We also found that Triol inhibited TNF-α-induced degradation of IκBα and phosphorylation of NF-κBp65 that are required for NF-κB activation. Furthermore, Triol significantly reversed TNF-α-induced down-expression of CYLD, which is a deubiquitinase that negatively regulates activation of NF-κB. These results suggest that Triol displays an anti-inflammatory effect on TNF-α-induced RBMECs via downregulating of CYLD-NF-κB signaling pathways and might have a potential benefit in therapeutic neuroinflammation related diseases.

  20. [The effect of disodium cromoglycate (DSCG) on infiltration of inflammatory cells into bronchial mucosa and on expression of adhesion molecules in asthmatics].

    PubMed

    Hoshino, M; Nakamura, Y

    1995-06-01

    We studied the effect of disodium cromoglycate (DSCG) used as a therapeutic drug for the treatment of bronchial asthma on infiltration of inflammatory cells into the bronchial mucosa and on the expression of adhesion molecules in asthmatic patients. Biopsies of the bronchial mucosa of 9 patients with atopic asthma were performed before and after the administration of an aerosol containing DSCG (8 mg/day). Staining with anti-EG2 antibody was made on the tissues obtained to determine the number of eosinophils, with anti-NP57 antibody to determine the number of neutrophils, with anti-AA1 antibody for mast cells, with anti-CD4, -CD8, -CD3 for T lymphocytes, and with anti-CD68 antibody for macrophages. Another staining was made to examine the expression of adhesion molecules including intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and endothelial leukocyte adhesion molecule-1 (ELAM-1) on the vascular endothelium and to determine the presence of P-selection. Moreover, the intensity of the expression of ICAM-1 on the bronchial epithelium was investigated. The number of eosinophils, mast cells, T lymphocytes and macrophages were significantly decreased, and the expression of ICAM-1, VCAM-1 and ELAM-1 were significantly inhibited by the administration of DSCG. There were significant correlations between ICAM-1 and the number of T lymphocytes, and between VCAM-1 and the number of eosinophils. These results suggest that DSCG inhibits the expression of adhesion molecules as an anti-inflammatory action, and decreases the number of inflammatory cells in the airways of asthmatic patients.

  1. Berberine reduces leukocyte adhesion to LPS-stimulated endothelial cells and VCAM-1 expression both in vivo and in vitro.

    PubMed

    Wu, Y-H; Chuang, S-Y; Hong, W-C; Lai, Y-J; Chang, G-J; Pang, J-H S

    2012-01-01

    Leukocyte adhesion to endothelium plays a critical initiating role in inflammation. Berberine, an anti-inflammatory natural compound, is known to attenuate lipopolysaccharide (LPS)-induced lung injury and improve survival of endotoxemic animals with mechanism not fully clarified. This study investigated the effects of berberine on the LPS-induced leukocyte-endothelial cell adhesion both in vivo and in vitro. We first established an animal model to observe the in vivo LPS-induced adhesion of leukocytes to the endothelium of venules in the lung tissue dose-dependently. Pretreatment of LPS-stimulated rats with berberine for 1 h reduced the leukocyte-endothelium adhesion and vascular cell adhesion molecule-1 (VCAM-1) expression in lung. Pretreatment of LPS-stimulated vascular endothelial cells with berberine also dose-dependently decreased the number of adhered THP-1 cells and VCAM-1 expression at both RNA and protein levels. Berberine was further confirmed to inhibit the nuclear translocation and DNA binding activity of LPS-activated nuclear factor-kappa B (NF-kappa B). These data demonstrated an additional molecular mechanism for the profound anti-inflammatory effect of berberine.

  2. Inhibition of tumor necrosis factor-{alpha}-induced expression of adhesion molecules in human endothelial cells by the saponins derived from roots of Platycodon grandiflorum

    SciTech Connect

    Kim, Ji Young; Kim, Dong Hee; Kim, Hyung Gyun; Song, Gyu-Yong; Chung, Young Chul; Roh, Seong Hwan; Jeong, Hye Gwang . E-mail: hgjeong@chosun.ac.kr

    2006-01-15

    Adhesion molecules play an important role in the development of atherogenesis and are produced by endothelial cells after being stimulated with various inflammatory cytokines. This study examined the effect of saponins that were isolated from the roots of Platycodon grandiflorum A. DC (Campanulaceae), Changkil saponins (CKS), on the cytokine-induced monocyte/human endothelial cell interaction, which is a crucial early event in atherogenesis. CKS significantly inhibited the TNF{alpha}-induced increase in monocyte adhesion to endothelial cells as well as decreased the protein and mRNA expression levels of vascular adhesion molecule-1 and intercellular cell adhesion molecule-1 on endothelial cells. Furthermore, CKS significantly inhibited the TNF{alpha}-induced production of intracellular reactive oxygen species (ROS) and activation of NF-{kappa}B by preventing I{kappa}B degradation and inhibiting I{kappa}B kinase activity. Overall, CKS has anti-atherosclerotic and anti-inflammatory activity, which is least in part the result of it reducing the cytokine-induced endothelial adhesion to monocytes by inhibiting intracellular ROS production, NF-{kappa}B activation, and cell adhesion molecule expression in endothelial cells.

  3. Daily consumption of grapefruit for 6 weeks reduces urine F2-isoprostanes in overweight adults with high baseline values but has no effect on plasma high-sensitivity C-reactive protein or soluble vascular cellular adhesion molecule 1.

    PubMed

    Dow, Caitlin A; Wertheim, Betsy C; Patil, Bhimanagouda S; Thomson, Cynthia A

    2013-10-01

    Individuals with obesity and metabolic syndrome (MetS) are at increased risk of cardiovascular disease, in part due to heightened inflammatory/oxidative processes. Results from epidemiologic and experimental studies suggest that citrus, and grapefruit in particular, may have a role in promoting vascular health, although clinical trial data are lacking. Here, we evaluated the anti-inflammatory/antioxidant effects of habitual grapefruit consumption in 69 overweight/obese men and women and in a subsample of participants with MetS (n = 29). Participants were randomly assigned to either a grapefruit group in which they consumed a low bioactive diet plus 1.5 grapefruit/d for 6 wk (n = 37, n = 14 with MetS) or to a control condition in which a low bioactive diet devoid of citrus was consumed (n = 32, n = 15 with MetS). Plasma soluble vascular adhesion molecule-1 (sVCAM-1), plasma high-sensitivity C-reactive protein (hsCRP), and urinary F2-isoprostanes were evaluated before and after the intervention phase. F2-isoprostane concentrations were not different in the grapefruit versus control arm after the intervention (12.4 ± 6.4 vs. 15.9 ± 9.0 ng/mg creatinine, P = 0.16), whereas plasma hsCRP concentrations tended to be lower in the grapefruit versus control arm postintervention (2.1 ± 1.5 vs. 2.8 ± 2.0 mg/L, P = 0.09). In adults with MetS, grapefruit consumption tended to result in lower postintervention F2-isoprostane concentrations compared with the control condition (12.0 ± 4.5 vs. 18.3 ± 10.9 ng/mg creatinine, P = 0.06). Furthermore, those with high baseline F2-isoprostane concentrations experienced significant reductions in this biomarker in response to grapefruit consumption (P = 0.021). Change in sVCAM-1 concentrations did not vary by treatment arm nor were there differences between arms postintervention. These results suggest that intake of grapefruit twice daily for 6 wk does not significantly reduce inflammation and oxidative stress, although there is a

  4. Negative Association of Circulating MicroRNA-126 with High-sensitive C-reactive Protein and Vascular Cell Adhesion Molecule-1 in Patients with Coronary Artery Disease Following Percutaneous Coronary Intervention

    PubMed Central

    Wang, Jun-Nan; Yan, You-You; Guo, Zi-Yuan; Jiang, Ya-Juan; Liu, Lu-Lu; Liu, Bin

    2016-01-01

    Background: Percutaneous coronary intervention (PCI) causes endothelial damage, resulting in an inflammatory response with elevation of markers such as high-sensitive C-reactive protein (hs-CRP) and vascular cell adhesion molecule-1 (VCAM-1), which are associated with restenosis after PCI. Evidence suggests that microRNA-126 (miR-126) plays an important role in vascular inflammation, but its correlation with PCI-mediated inflammation has not been investigated. In this study, we investigated the effect of PCI on circulating miR-126 and inflammation markers such as hs-CRP and VCAM-1. Methods: We enrolled 130 patients with coronary artery disease (CAD) in the Second Hospital of Jilin University from October 2015 to December 2015. Among them, 82 patients with CAD, defined as at least one major epicardial vessel with >70% stenosis who planned to undergo PCI, were divided into acute coronary syndrome (ACS) group (46 patients) and stable angina (SA) group (36 patients). Forty-eight patients confirmed by coronary angiography without PCI were used as controls. The plasmas of all patients were collected prior to PCI and at 30 min, 24 h, and 72 h after PCI. The plasma VCAM-1 and hs-CRP were detected by enzyme-linked immunosorbent assay, and the miR-126 was evaluated by quantitative reverse transcription-polymerase chain reaction. Results: Plasma concentrations of hs-CRP and VCAM-1 in patients with either ACS (n = 46) or SA (n = 36) were significantly higher than in controls (n = 48) (P < 0.01) prior to PCI, and increased further at 24 h and 72 h after PCI, compared with prior PCI. Moreover, VCAM-1 was positively correlated with balloon time and pressure. In contrast, the plasma concentration of miR-126 was significantly lower in patients with CAD than in controls, and further decreased with time post-PCI. A negative correlation was observed between miR-126 and hs-CRP and VCAM-1 at 72 h after PCI. Conclusion: There was a negative correlation of miR-126 with the PCI

  5. Resistance to cerebral malaria in tumor necrosis factor-alpha/beta-deficient mice is associated with a reduction of intercellular adhesion molecule-1 up-regulation and T helper type 1 response.

    PubMed Central

    Rudin, W.; Eugster, H. P.; Bordmann, G.; Bonato, J.; Müller, M.; Yamage, M.; Ryffel, B.

    1997-01-01

    Tumor necrosis factor (TNF) induced by Plasmodium berghei ANKA (PbA) infection was suggested to play an important role in the development of cerebral malaria (CM). We asked whether TNF-alpha/beta double-deficient mice, which have a complete disruption of the TNF-signaling pathways, are protected from CM and what might be the possible mechanisms of protection. PbA infection induces fatal CM in wild-type mice, which die within 5 to 8 days with severe neurological signs. In contrast, TNF-alpha/beta-deficient mice are completely resistant to PbA-induced CM. As PbA-induced up-regulation of endothelial intercellular adhesion molecule (ICAM)-1 expression as well as the systemic release of nitric oxide is found only in wild-type mice, TNF is apparently central for the recruitment of mononuclear cells and microvascular damage. Mononuclear cell adhesion to the endothelium, vascular leak and, perivascular hemorrhage are found only in the brain of wild-type mice. By contrast, the development of parasitemia and anemia is independent of TNF. Resistance to CM in TNF-alpha/beta-deficient mice is associated with reduced interferon-gamma and interleukin-12 expression in the brain, in the absence of increased T helper type 2 cytokines. In conclusion, TNF apparently is required for PbA-induced endothelial ICAM-1 up-regulation and subsequent microvascular pathology resulting in fatal CM. In the absence of TNF, ICAM-1 and nitric oxide up-regulation are reduced, and PbA infection fails to cause fatal CM. Images Figure 3 Figure 4 Figure 5 Figure 6 PMID:9006341

  6. [Effects of crocetin on VCAM-1 expression in human umbilical vein endothelial cells and monocyte-endothelial cell adhesion].

    PubMed

    Zheng, Shu-guo; Zhao, Meng-qiu; Ren, You-nan; Yang, Jie-ren; Qian, Zhi-yu

    2015-01-01

    Crocetin, a naturally occurring carotenoid, possesses antioxidant and antiatherosclerotic properties, of which the underlying mechanism remains unclear. In the present study, we examined the effects of crocetin (0.1, 1, 10 μmol·L(-1)) on angiotensin II (Ang II, 0.1 μmol·L(-1)) induced expression of vascular cell adhesion molecule-1 (VCAM-1) in human umbilical vein endothelial cells (HUVECs) and monocyte-endothelial cell adhesion. The effects of crocetin on the activation of nuclear factor kappa B (NF-κB) and intracellular reactive oxygen species (ROS) were also observed. The results demonstrated that crocetin notably suppressed Ang II induced NF-κB activation (P<0.01) and VCAM-1 expression (P<0.05, P<0.01) in HUVECs, accompanied by a markedly reduced monocyte-endothelial cell adhesion (P<0.05, P<0.01). In addition, preincubation with crocetin resulted in a significant enhancement of cellular antioxidant capacity (P<0.05, P<0.01), while Ang II induced intracellular ROS decreased markedly (P<0.05, P<0.01). These results indicated that crocetin was capable of suppressing Ang II induced VCAM-1 expression and monocyte-endothelial cell adhesion by suppression of NF-κB activation, which might be derived from the enhancement of antioxidant capacity and subsequent reduction of intracellular ROS.

  7. Borrelia burgdorferi upregulates expression of adhesion molecules on endothelial cells and promotes transendothelial migration of neutrophils in vitro.

    PubMed Central

    Sellati, T J; Burns, M J; Ficazzola, M A; Furie, M B

    1995-01-01

    The accumulation of leukocytic infiltrates in perivascular tissues is a key step in the pathogenesis of Lyme disease, a chronic inflammatory disorder caused by Borrelia burgdorferi. During an inflammatory response, endothelial cell adhesion molecules mediate the attachment of circulating leukocytes to the blood vessel wall and their subsequent extravasation into perivascular tissues. Using cultured human umbilical vein endothelial cells (HUVEC) in a whole-cell enzyme-linked immunosorbent assay, we demonstrated that B. burgdorferi activated endothelium in a dose- and time-dependent fashion as measured by upregulation of the adhesion molecules E-selectin, vascular cell adhesion molecule 1 (VCAM-1), and intercellular adhesion molecule 1 (ICAM-1). As few as one spirochete per endothelial cell stimulated increased expression of these molecules. Expression of E-selectin peaked after spirochetes and HUVEC were coincubated for 4 h and returned to near-basal levels by 24 h. In contrast, expression of VCAM-1 and ICAM-1 peaked at 12 h and remained elevated at 24 h. HUVEC monolayers cultured on acellular amniotic tissue were used to investigate the consequences of endothelial cell activation by spirochetes. After incubation of HUVEC-amnion cultures with B. burgdorferi, subsequently added neutrophils migrated across the endothelial monolayers. This process was mediated by E-selectin and by CD11/CD18 leukocytic integrins. The extent of migration depended on both the number of spirochetes used to stimulate the HUVEC and the length of the coincubation period. These results raise the possibility that B. burgdorferi induces a host inflammatory response and accompanying perivascular damage through activation of vascular endothelium. PMID:7591083

  8. Glossogyne tenuifolia Extract Inhibits TNF-α-Induced Expression of Adhesion Molecules in Human Umbilical Vein Endothelial Cells via Blocking the NF-kB Signaling Pathway.

    PubMed

    Hsuan, Chin-Feng; Hsu, Hsia-Fen; Tseng, Wei-Kung; Lee, Thung-Lip; Wei, Yu-Feng; Hsu, Kwan-Lih; Wu, Chau-Chung; Houng, Jer-Yiing

    2015-09-17

    Chronic inflammation plays a pivotal role in the development of atherosclerosis, where the pro-inflammatory cytokine-induced expression of endothelial adhesion molecules and the recruitment of monocytes are the crucial events leading to its pathogenesis. Glossogyne tenuifolia ethanol extract (GTE) is shown to have potent anti-inflammatory and antioxidant activities. We evaluated the effects of GTE and its major components, luteolin (lut), luteolin-7-glucoside (lut-7-g), and oleanolic acid (OA) on TNF-α-induced expression of adhesion molecules in human umbilical vein endothelial cells (HUVECs). The results demonstrated that GTE, lut, and lut-7-g attenuated the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in TNF-α-activated HUVECs, and inhibited the adhesion of monocytes to TNF-α-activated HUVECs. The TNF-α-induced mRNA expression of ICAM-1 and VCAM-1 was also suppressed, revealing their inhibitory effects at the transcriptional level. Furthermore, GTE, lut, and lut-7-g blocked the TNF-α-induced degradation of nuclear factor-kB inhibitor (IkB), an indicator of the activation of nuclear factor-kB (NF-kB). In summary, GTE and its bioactive components were effective in preventing the adhesion of monocytes to cytokine-activated endothelium by the inhibition of expression of adhesion molecules, which in turn is mediated through blocking the activation and nuclear translocation of NF-kB. The current results reveal the therapeutic potential of GTE in atherosclerosis.

  9. HOXA9 Methylation by PRMT5 Is Essential for Endothelial Cell Expression of Leukocyte Adhesion Molecules

    PubMed Central

    Bandyopadhyay, Smarajit; Harris, Daniel P.; Adams, Gregory N.; Lause, Gregory E.; McHugh, Anne; Tillmaand, Emily G.; Money, Angela; Willard, Belinda; Fox, Paul L.

    2012-01-01

    The induction of proinflammatory proteins in stimulated endothelial cells (EC) requires activation of multiple transcription programs. The homeobox transcription factor HOXA9 has an important regulatory role in cytokine induction of the EC-leukocyte adhesion molecules (ELAM) E-selectin and vascular cell adhesion molecule 1 (VCAM-1). However, the mechanism underlying stimulus-dependent activation of HOXA9 is completely unknown. Here, we elucidate the molecular mechanism of HOXA9 activation by tumor necrosis factor alpha (TNF-α) and show an unexpected requirement for arginine methylation by protein arginine methyltransferase 5 (PRMT5). PRMT5 was identified as a TNF-α-dependent binding partner of HOXA9 by mass spectrometry. Small interfering RNA (siRNA)-mediated depletion of PRMT5 abrogated stimulus-dependent HOXA9 methylation with concomitant loss in E-selectin or VCAM-1 induction. Chromatin immunoprecipitation analysis revealed that PRMT5 is recruited to the E-selectin promoter following transient HOXA9 binding to its cognate recognition sequence. PRMT5 induces symmetric dimethylation of Arg140 on HOXA9, an event essential for E-selectin induction. In summary, PRMT5 is a critical coactivator component in a newly defined, HOXA9-containing transcription complex. Moreover, stimulus-dependent methylation of HOXA9 is essential for ELAM expression during the EC inflammatory response. PMID:22269951

  10. Expression of Inflammation-related Intercellular Adhesion Molecules in Cardiomyocytes In Vitro and Modulation by Pro-inflammatory Agents.

    PubMed

    El-Battrawy, Ibrahim; Tülümen, Erol; Lang, Siegfried; Akin, Ibrahim; Behnes, Michael; Zhou, Xiabo; Mavany, Martin; Bugert, Peter; Bieback, Karen; Borggrefe, Martin; Elmas, Elif

    2016-01-01

    Cell-surface adhesion molecules regulate multiple intercellular and intracellular processes and play important roles in inflammation by facilitating leukocyte endothelial transmigration. Whether cardiomyocytes express surface-adhesion molecules related to inflammation and the effect of pro-inflammatory mediators remain unknown. In the present study, the expression of different cell-adhesion molecules (CD11a, CD11b, CD31, CD62P, CD162, F11 receptor and mucosal vascular addressin cell adhesion molecule 1 (MADCAM1)) and the effect of pro-inflammatory mediators were investigated in an in vitro model of human cardiomyocytes. Cells were supplied as a primary culture of cardiac alpha actin-positive cells from human heart tissue. The cells were incubated for 24 h with 1 U/ml thrombin or 700 ng/ml lipopolysaccharide (LPS) or with a combination of both. The expression of the cell adhesion molecules was measured by flow cytometry. In cultured human cardiomyocytes, 22.8% of cells expressed CD31, 7.1% MADCAM1 and 2.6% F11R. CD11a, CD11b, CD62P and CD162 were expressed by fewer than 2% of the cells at baseline. CD31 expression increased on incubation of cardiomyocytes with thrombin by 26% (p<0.05) and with LPS by 26% (p=0.06). The combination of thrombin and LPS did not result in increased levels of CD31 (p>0.10). The pro-inflammatory agents LPS and thrombin had no effect on the expression of MADCAM1 and F11R. Inflammation-related cell-adhesion molecules CD31, MADCAM1 and F11R were shown to be expressed on the surface of human cardiomyocytes in an in vitro model. Incubation with LPS or thrombin resulted in increased expression of CD31, however, it did not modify the expression of the cell adhesion molecules MADCAM1 and F11R. Copyright © 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  11. Effects of benidipine, a dihydropyridine-Ca2+ channel blocker, on expression of cytokine-induced adhesion molecules and chemoattractants in human aortic endothelial cells.

    PubMed

    Matsubara, Masahiro; Hasegawa, Kazuhide

    2004-09-13

    Benidipine hydrochloride (benidipine) is a dihydropyridine-Ca2+ channel blocker with antioxidant properties. We examined the effects of benidipine on cytokine-induced expression of adhesion molecules and chemokines, which play important roles in the adhesion of monocytes to endothelium. Pretreatment of human aortic endothelial cells (HAECs) with benidipine (0.3-10 micromol/l) for 24 h significantly suppressed cytokine-induced vascular cell adhesion molecule-1 (VCAM-1) and intracellular cell adhesion molecule-1 (ICAM-1) mRNA and protein expression, resulting in reduced adhesion of THP-1 monocytes. Benidipine also suppressed induction of monocyte chemoattractant protein (MCP)-1 and interleukin-8. Benidipine inhibited redox-sensitive transcriptional nuclear factor-kappaB (NF-kappaB) pathway, as determined by Western blotting of inhibitory kappaB (IkappaB) phosphorylation and luciferase reporter assay. Results of analysis using optical isomers of benidipine and antioxidants suggested that these inhibitory effects were dependent on pharmacological effects other than Ca2+ antagonism such as antioxidant effects. Benidipine may thus have anti-inflammatory properties and benefits for in the treatment of atherosclerosis.

  12. Manassantin A and B isolated from Saururus chinensis inhibit TNF-alpha-induced cell adhesion molecule expression of human umbilical vein endothelial cells.

    PubMed

    Kwon, Oh Eok; Lee, Hyun Sun; Lee, Seung Woong; Chung, Mi Yeon; Bae, Ki Hwan; Rho, Mun-Chual; Kim, Young-Kook

    2005-01-01

    Leukocyte adhesion to the vascular endothelium is a critical initiating step in inflammation and atherosclerosis. We have herein studied the effect of manassantin A (1) and B (2), dineolignans, on interaction of THP-1 monocytic cells and human umbilical vein endothelial cells (HUVEC) and expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin in HUVEC. When HUVEC were pretreated with 1 and 2 followed by stimulation with TNF-alpha, adhesion of THP-1 cells to HUVEC decreased in dose-dependent manner with IC50 values of 5 ng/mL and 7 ng/mL, respectively, without cytotoxicity. Also, 1 and 2 inhibited TNF-alpha-induced up-regulation of ICAM-1, VCAM-1 and E-selectin. The present findings suggest that 1 and 2 prevent monocyte adhesion to HUVEC through the inhibition of ICAM-1, VCAM-1 and E-selectin expression stimulated by TNF-alpha, and may imply their usefulness for the prevention of atherosclerosis relevant to endothelial activation.

  13. [Neutrophils expression of adhesion molecules in diabetic nephropaty patients].

    PubMed

    Shcherban', T D

    2013-01-01

    CD11b and CD54 expression on neutrophils in patients with diabetic nephropathy (DN), arterial hypertension patients and healthy donors were examined. Development of DN associates with an increase of the number of CD11b and CD54 positive cells and violation of cellular co-operation. In the conditions of diabetic microenvironment expression of adhesion molecules rises substantially, what may characterized the mechanism of connection between hyperglycemia and vascular and tissues injury at DN. Authentication of morphological and biochemical markers of intercellular co-operation must in a prospect assist the deeper understanding of pathogenic mechanisms of DN.

  14. Adhesion

    MedlinePlus

    ... the intestines, adhesions can cause partial or complete bowel obstruction . Adhesions inside the uterine cavity, called Asherman syndrome , ... 1. Read More Appendicitis Asherman syndrome Glaucoma Infertility Intestinal obstruction Review Date 4/5/2016 Updated by: Irina ...

  15. Adhesions

    MedlinePlus

    Adhesions are bands of scar-like tissue. Normally, internal tissues and organs have slippery surfaces so they can shift easily as the body moves. Adhesions cause tissues and organs to stick together. They ...

  16. Reduced immunohistochemical expression of adhesion molecules in vitiligo skin biopsies.

    PubMed

    Reichert Faria, Adriane; Jung, Juliana Elizabeth; Silva de Castro, Caio César; de Noronha, Lucia

    2017-03-01

    Because defects in adhesion impairment seem to be involved in the etiopathogenesis of vitiligo, this study aimed to compare the immunohistochemical expression of several adhesion molecules in the epidermis of vitiligo and non lesional vitiligo skin. Sixty-six specimens of lesional and non lesional skin from 33 volunteers with vitiligo were evaluated by immunohistochemistry using anti-beta-catenin, anti-E-cadherin, anti-laminin, anti-beta1 integrin, anti-collagen IV, anti-ICAM-1 and anti-VCAM-1 antibodies. Biopsies of vitiligo skin demonstrated a significant reduction in the expression of laminin and integrin. The average value of the immunohistochemically positive reaction area of the vitiligo specimens was 3053.2μm(2), compared with the observed value of 3431.8μm(2) in non vitiligo skin (p=0.003) for laminin. The immuno-positive area was 7174.6μm(2) (vitiligo) and 8966.7μm(2) (non lesional skin) for integrin (p=0.042). A reduction in ICAM-1 and VCAM-1 expression in the basal layer of the epidermis in vitiligo samples was also observed (p=0.001 and p<0.001, respectively). However, no significant differences were observed with respect to the expression of beta-catenin, E-cadherin, and collagen IV between vitiligo and non lesional skin. Our results suggest that an impairment in adhesion exists in vitiligo skin, which is supported by the diminished immunohistochemical expression of laminin, beta1 integrin, ICAM-1 and VCAM-1. Copyright © 2017 Elsevier GmbH. All rights reserved.

  17. KDM4B histone demethylase and G9a regulate expression of vascular adhesion proteins in cerebral microvessels

    PubMed Central

    Choi, Ji-Young; Yoon, Sang-Sun; Kim, Sang-Eun; Ahn Jo, Sangmee

    2017-01-01

    Intercellular adhesion molecule 1 (ICAM1) mediates the adhesion and transmigration of leukocytes across the endothelium, promoting inflammation. We investigated the epigenetic mechanism regulating ICAM1 expression. The pro-inflammatory cytokine TNF-α dramatically increased ICAM1 mRNA and protein levels in human brain microvascular endothelial cells and mouse brain microvessels. Chromatin immunoprecipitation revealed that TNF-α reduced methylation of histone H3 at lysines 9 and 27 (H3K9 and H3K27), well-known residues involved in gene suppression. Inhibition of G9a and EZH2, histone methyltransferases responsible for methylation at H3K9 and H3K27, respectively as well as G9a overexpression demonstrated the involvement of G9a in TNF-α-induced ICAM1 expression and leukocyte adhesion and transmigration. A specific role for KDM4B, a histone demethylase targeting H3K9me2, in TNF-α-induced ICAM1 upregulation was validated with siRNA. Moreover, treating mice with a KDM4 inhibitor ML324 blocked TNF-α-mediated neutrophil adhesion. Similarly, TNF-α-induced VCAM1 expression was suppressed by G9a overexpression and KDM4B knockdown. Collectively, we demonstrated that modification of H3K9me2 by G9a and KDM4B regulates expression of vascular adhesion molecules, and that depletion of these proteins or KDM4B reduces inflammation-induced leukocyte extravasation. Thus, blocking ICAM1 or KDM4B could offer a novel therapeutic opportunity treating brain diseases. PMID:28327608

  18. Adhesion molecules in vernal keratoconjunctivitis

    PubMed Central

    El-Asrar, A.; Geboes, K.; Al-Kharashi, S.; Tabbara, K.; Missotten, L.; Desmet, V.

    1997-01-01

    AIMS/BACKGROUND—Adhesion molecules play a key role in the selective recruitment of different leucocyte population to inflammatory sites. The purpose of the present study was to investigate the presence and distribution of adhesion molecules in the conjunctiva of patients with vernal keratoconjunctivitis (VKC).
METHODS—The presence and distribution of adhesion molecules were studied in 14 conjunctival biopsy specimens from seven patients with active VKC and in four normal conjunctival biopsy specimens. We used a panel of specific monoclonal antibodies (mAbs) directed against intercellular adhesion molecule-1 (ICAM-1), intercellular adhesion molecule-3 (ICAM-3), lymphocyte function associated antigen-1 (LFA-1), very late activation antigen-4 (VLA-4), vascular cell adhesion molecule-1 (VCAM-1), and endothelial leucocyte adhesion molecule-1 (ELAM-1). In addition, a panel of mAbs were used to characterise the composition of the inflammatory infiltrate.
RESULTS—In the normal conjunctiva, ICAM-1 was expressed on the vascular endothelium only, LFA-1 and ICAM-3 on epithelial and stromal mononuclear cells , and VLA-4 on stromal mononuclear cells. The expression of VCAM-1 and ELAM-1 was absent. The number of cells expressing adhesion molecules was found to be markedly increased in all VKC specimens. This was concurrent with a heavy inflammatory infiltrate. Strong ICAM-1 expression was induced on the basal epithelial cells, and vascular endothelial cells. Furthermore, ICAM-1 was expressed on stromal mononuclear cells. LFA-1 and ICAM-3 were expressed on the majority of epithelial and stromal infiltrating mononuclear cells. VLA-4 expression was noted on stromal mononuclear cells. Compared with controls, VKC specimens showed significantly more ICAM-3+, LFA-1+, and VLA-4+ cells. VCAM-1 and ELAM-1 were induced on the vascular endothelial cells.
CONCLUSIONS—Increased expression of adhesion molecules may play an important role in the pathogenesis of VKC.

 PMID

  19. Rolling adhesion kinematics of yeast engineered to express selectins.

    PubMed

    Bhatia, Sujata K; Swers, Jeffrey S; Camphausen, Raymond T; Wittrup, K Dane; Hammer, Daniel A

    2003-01-01

    Selectins are cell adhesion molecules that mediate capture of leukocytes on vascular endothelium as an essential component of the inflammatory response. Here we describe a method for yeast surface display of selectins, together with a functional assay that measures rolling adhesion of selectin-expressing yeast on a ligand-coated surface. E-selectin-expressing yeast roll specifically on surfaces bearing sialyl-Lewis-x ligands. Observation of yeast rolling dynamics at various stages of their life cycle indicates that the kinematics of yeast motion depends on the ratio of the bud radius to the parent radius (B/P). Large-budded yeast "walk" across the surface, alternately pivoting about bud and parent. Small-budded yeast "wobble" across the surface, with bud pivoting about parent. Tracking the bud location of budding yeast allows measurement of the angular velocity of the yeast particle. Comparison of translational and angular velocities of budding yeast demonstrates that selectin-expressing cells are rolling rather than slipping across ligand-coated surfaces.

  20. Simvastatin inhibits the expression of inflammatory cytokines and cell adhesion molecules induced by LPS in human dental pulp cells.

    PubMed

    Jung, J Y; Woo, S M; Kim, W J; Lee, B N; Nör, J E; Min, K S; Choi, C H; Koh, J T; Lee, K J; Hwang, Y C

    2017-04-01

    To investigate the effect of simvastatin on lipopolysaccharide (LPS)-stimulated inflammatory cytokines, cell adhesion molecules and nuclear factor-κB (NF-κB) transcription factors in human dental pulp cells (HDPCs). The effect of LPS and simvastatin on human dental pulp cell (HDPCs) viability was measured using a 3-[4, 5-dimethylthiazol-2-yl]-2, 5 diphenyltetrazolium bromide (MTT) assay. The expression of inflammatory cytokines and cell adhesion molecules was evaluated by reverse-transcription polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA) and Western blot analysis. NF-κB transcription factors were evaluated by Western blot analysis. Statistical analysis was performed with analysis of variance (anova). The viability of cells exposed to different concentrations of E. coli LPS, P. gingivalis LPS and simvastatin was not significantly different compared with that of control cells (P > 0.05). LPS significantly increased interleukin (IL)-1β (P < 0.05) and IL-6 mRNA expression (P < 0.05) and vascular cell adhesion molecule-1 (VCAM-1) (P < 0.05) and intercellular adhesion molecule-1 (ICAM-1) protein expression (P < 0.05) in HDPCs. Treatment with simvastatin significantly attenuated LPS-stimulated production of IL-1β, IL-6, VCAM-1 and ICAM-1 (P < 0.05). Treatment with simvastatin decreased LPS-induced expression of p65 and phosphorylation of IκB and also significantly decreased the phosphorylation of p65 and IκB in the cytoplasm and the level of p65 in the nucleus (P < 0.05). Simvastatin has a suppressing effect on LPS-induced inflammatory cytokine, cell adhesion molecules and NF-κB transcription factors in HDPCs. Therefore, simvastatin might be a useful candidate as a pulp-capping agent in vital pulp therapy. © 2016 International Endodontic Journal. Published by John Wiley & Sons Ltd.

  1. Inhibitory effect of butein on tumor necrosis factor-α-induced expression of cell adhesion molecules in human lung epithelial cells via inhibition of reactive oxygen species generation, NF-κB activation and Akt phosphorylation.

    PubMed

    Jang, Ji Hoon; Yang, Eun Sun; Min, Kyoung-Jin; Kwon, Taeg Kyu

    2012-12-01

    Cell adhesion molecules play an important role in inflammatory response, angiogenesis and tumor progression. Butein (tetrahydroxychalcone) is a small molecule from natural sources, known to be a potential therapeutic drug with anti-inflammatory, anticancer and antioxidant activities. In the present study, we investigated the inhibitory effect of butein on tumor necrosis factor (TNF)-α-induced adhesion molecule expression and its molecular mechanism of action. Butein significantly decreased TNF-α-induced monocyte (U937) cell adhesion to lung epithelial cells in a dose-dependent manner. Butein also inhibited the protein and mRNA expression of intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in TNF-α-stimulated A549 human lung epithelial cells in a dose-dependent manner. Butein inhibited TNF-α-induced reactive oxygen species (ROS) generation and nuclear factor-κB (NF-κB) activation in A549 cells; it also inhibited the phosphorylation of MAPKs and Akt, suggesting that the MAPK/Akt signaling pathway may be involved in the butein-mediated inhibition of TNF-α-induced leukocyte adhesion to A549 cells. Collectively, our results suggest that butein affects cell adhesion through the inhibition of TNF-α-induced ICAM-1 and VCAM-1 expression by inhibiting the NF-κB/MAPK/Akt signaling pathway and ROS generation, thereby, elucidating the role of butein in the anti-inflammatory response.

  2. Effect of bamboo culm extract on oxidative stress and genetic expression: bamboo culm extract ameliorates cell adhesion molecule expression and NFkappaB activity through the suppression of the oxidative stress.

    PubMed

    Lee, Min-Ja; Park, Won-Hwan; Song, Young-Sun; Lee, Yong-Woo; Song, Yeong-Ok; Moon, Gap-Soon

    2008-10-01

    This study was designed to investigate whether bamboo culm extract (BCE) supplementation may ameliorate risk factors of cardiovascular diseases, such as hypercholesterolemia. Oxidative stress and inflammatory mediators in plasma, livers of C57BL/6 mice fed high-cholesterol diet and calf pulmonary artery endothelial (CPAE) cells. Briefly, C57BL/6 mice were fed the high-cholesterol diet which was supplemented with 1% (w/w), or 3% (w/w) of BCE for 16 weeks. The concentration of total cholesterol, LDL-cholesterol, HDL-cholesterol level and atherogenic index were measured. Plasma TEAC value, hepatic thiobarbituric acid reactive substances (TBARS), protein carbonyl values and hepatic antioxidant enzyme activities, such as Cu,Zn-superoxide dismutase (SOD), Mn-SOD, glutathione peroxidase (GSH-Px), GSH reductase and catalase were determined. In addition, hepatic nuclear factor kappa B activities were detected. In the calf pulmonary artery endothelial (CPAE) cells stimulated with lipopolysaccharide, the expression of vascular cell adhesion molecule-1 (VCAM-1) and intracellular cell adhesion molecule-1 (ICAM-1) were measured. Plasma cholesterol level was decreased, while HDL-cholesterol was increased, thus atherogenic index was lowered in BCE-supplemented animals. Plasma trolox equivalent and hepatic thiobarbituric acid reactive substances and protein carbonyl values were lowered significantly in BCE groups (p<0.05) in a dose-dependent manner. Hepatic antioxidative enzyme activities, such as Cu,Zn-superoxide dismutase (SOD), Mn-SOD, glutathione peroxidase (GSH-P), GSH reductase, and catalase were elevated in mice fed BCE-supplemented diets (p<0.05). Nuclear factor kappa B activities of livers and vascular cell adhesion molecule-1 and intracellular cell adhesion molecule-1 expressions in CPAE cells stimulated with lipopolysaccharide were significantly lowered in BCE groups (p<0.05). These results suggest that BCE supplementation may modulate lipoprotein composition and

  3. Telmisartan attenuates hyperglycemia-exacerbated VCAM-1 expression and monocytes adhesion in TNFα-stimulated endothelial cells by inhibiting IKKβ expression.

    PubMed

    Song, Kee-Ho; Park, Jung-Hyun; Jo, Inho; Park, Joong-Yeol; Seo, Jungwon; Kim, Soon Ae; Cho, Du-Hyong

    2016-03-01

    Uncontrolled hyperglycemia accelerates endothelial damage and vascular inflammation caused by proinflammatory cytokines including tumor necrosis factor α (TNFα), which leads to arteriosclerotic cardiovascular diseases such as myocardial infarction. Telmisartan, an angiotensin II type 1 receptor blocker (ARB), is prescribed for treatment of hypertensive patients with concurrent diabetes mellitus (DM). Although a few clinical trials have suggested that telmisartan decreases cardiovascular complications in diabetic patients, the molecular mechanism for the beneficial effects remains elusive. Here, we investigated a molecular mechanism and effects of telmisartan on the expression of vascular cell adhesion molecule-1 (VCAM-1) and attachment of monocytes onto endothelial cells induced by TNFα in hyperglycemia-treated bovine aortic endothelial cells (BAEC). Telmisartan dose-dependently decreased hyperglycemia-aggravated IκB kinase β (IKKβ) expression and nuclear factor-κB (NF-κB) p65-Ser(536) phosphorylation, which accompanied a decrease in VCAM-1 expression and THP-1 monocytes adhesion. Among ARBs, including losartan and fimasartan, only telmisartan showed the inhibitory effects on expression of VCAM-1 and IKKβ, and phosphorylation of NF-κB p65-Ser(536). The telmisartan's beneficial effects were not changed by pretreatment with GW9662, a specific and irreversible peroxisome proliferator-activated receptor γ (PPARγ) antagonist, although GW9662 clearly inhibited rosiglitazone-induced CD36 expression. Finally, ectopic expression of wild type (WT)-IKKβ significantly restored telmisartan-attenuated VCAM-1 expression, NF-κB p65-Ser(536) phosphorylation, and THP-1 monocytes adhesion. Taken together, our findings demonstrate that telmisartan ameliorates hyperglycemia-exacerbated vascular inflammation, at least in part, by decreasing expression of IKKβ and VCAM-1 independently of PPARγ. Telmisartan may be useful for the treatment of DM-associated vascular

  4. Cell adhesion markers are expressed by a stable human endothelial cell line transformed by the SV40 large T antigen under vimentin promoter control.

    PubMed

    Vicart, P; Testut, P; Schwartz, B; Llorens-Cortes, C; Perdomo, J J; Paulin, D

    1993-10-01

    Markers of endothelium have been studied in a new endothelial cell line derived from human umbilical cord vein cells by microinjection of a recombinant gene that includes a deletion mutant of the human vimentin gene regulatory region controlling the large T and small t antigen coding region of the SV40 virus. In culture, this immortalized venous endothelial cell line (IVEC) demonstrated morphological characteristics of endothelium; uptake of acetylated low density lipoprotein and presence of the Factor VIII-related antigen. Treatment of IVEC cells with Interleukin-1 beta (IL-1 beta) at 10 U.ml-1 activates the expression of cell adhesion molecules such as endothelial leucocyte adhesion molecule (ELAM-1), intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1), as observed in primary culture. Prostacyclin secretion was induced in the IVEC cells by 100 nM PMA treatment and thrombin at 0.5 U/ml. Angiotensin converting enzyme (ACE) activity detected in IVEC cells was present but lower than ACE activity in primary endothelial cells and was completely blocked by enalaprilat (1 microM), a specific ACE inhibitor. The presence of ACE mRNA was also demonstrated in IVEC cells by RT-PCR amplification. Our data demonstrate that endothelial cells immortalized by use of this recombinant gene retain the morphological organization and numerous differentiated properties of endothelium.

  5. Effect of propane-2-sulfonic acid octadec-9-enyl-amide on the expression of adhesion molecules in human umbilical vein endothelial cells.

    PubMed

    Chen, Cai-Xia; Yang, Li-Chao; Xu, Xu-Dong; Wei, Xiao; Gai, Ya-Ting; Peng, Lu; Guo, Han; Hao-Zhou; Wang, Yi-Qing; Jin, Xin

    2015-06-05

    Oleoylethanolamide (OEA), an endogenous agonist of PPARα, has been reported to have anti-atherosclerotic properties. However, OEA can be enzymatically hydrolyzed to oleic acid and ethanolamine and, thus, is not expected to be orally active. In the present study, we designed and synthesized an OEA analog, propane-2-sulfonic acid octadec-9-enyl-amide (N15), which is resistant to enzymatic hydrolysis. The purpose of this study was to investigate the effects of N15 on the expression of adhesion molecules in human umbilical vein endothelial cells (HUVECs). The results showed that N15 inhibited TNFα-induced production of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 and the adhesion of monocytes to TNFα-induced HUVECs. Furthermore, the protective effect of N15 on inflammation is dependent upon a PPAR-α/γ-mediated mechanism. In conclusion, N15 protects against TNFα-induced vascular endothelial inflammation. This anti-inflammatory effect of N15 is dependent on PPAR-α/γ dual targets.

  6. Activation of nuclear factor-kappa B and cell adhesion molecule mRNA expression in duodenal mucosa of dogs with lymphocytic-plasmacytic enteritis.

    PubMed

    Okanishi, Hiroki; Kabeya, Hidenori; Maruyama, Soichi; Kagawa, Yumiko; Watari, Toshihiro

    2013-08-15

    Lymphocytic-plasmacytic enteritis (LPE) is the most common form of inflammatory bowel disease (IBD) affecting the canine small intestine; however, the molecular basis of the pathogenesis remains unclear. It has recently been hypothesized that the primary defect is impaired innate immune function, as is the case for human IBD. Nuclear factor-kappa B (NFkappaB) plays a central role in innate immunity, and is a major transcriptional regulator of several proinflammatory cytokines, pattern recognition receptors (PRRs) such as toll-like receptors (TLRs), nucleotide-binding oligomerization domain-like receptors and cell adhesion molecules (CAMs). The purpose of this study was to evaluate, in the duodenal mucosa of 21 dogs with LPE and 8 control dogs, the degree of NFkappaB activity and the mRNA expression of two selected cytokines, nucleotide oligomerization domain two (NOD2) receptor and three selected CAMs, all of which are regulated by NFkappaB, using the electrophoretic mobility shift assay and real-time reverse transcription PCR. NFkappaB binding activity was significantly higher in the inflamed duodenal mucosa of the LPE dogs as compared to healthy controls. Furthermore, expression of mRNA for intercellular cell adhesion molecule 1 (ICAM-1) and mucosal addressin cell adhesion molecule 1 (MAdCAM-1) was significantly higher and vascular cell adhesion molecule 1 (VCAM-1) mRNA significantly lower in LPE dogs than in healthy controls. However, there was no significant difference in the mRNA levels for TNFα, IL1β and NOD2 between the two groups. These results suggest that NFkappaB and CAMs may play important roles in the pathogenesis of canine LPE. Copyright © 2013 Elsevier B.V. All rights reserved.

  7. Soluble platelet selectin (sP-selectin) and soluble vascular cell adhesion molecule-1 (sVCAM-1) decrease during therapy with benznidazole in children with indeterminate form of Chagas' disease

    PubMed Central

    Laucella, S A; Segura, E L; Riarte, A; Sosa, Estani S

    1999-01-01

    The immune response against Trypanosoma cruzi infection has been associated with both protection and pathogenesis. Central events in host defence system- and immune-mediated damage are tightly regulated by cell adhesion molecules (CAM). Levels of sP-selectin and sVCAM-1 were measured in sera from 41 children with the indeterminate phase of Chagas' disease. Simultaneously, levels of soluble adhesion molecule were also quantified in Chagas' disease children undergoing specific chemotherapy with benznidazole. Levels of sP-selectin and sVCAM-1 were found to be elevated in children with indeterminate Chagas' disease before aetiologic therapy was started. However, a small group of patients showed sP-selectin and sVCAM-1 levels comparable to those of non-infected children. A positive correlation between levels of sVCAM-1 and sP-selectin in sera from Chagas' disease patients was found. There was a significantly greater decrease in the titres of sP-selectin and sVCAM-1 in those children receiving benznidazole therapy compared with those children receiving placebo. Measurement of soluble adhesion molecules revealed differences in the activation of the immune system in children with the indeterminate form of Chagas' disease. The early decrease of sP-selectin and sVCAM-1 levels after anti-parasitic treatment suggests that these molecules might be valuable indicators of effective parasitologic clearance. PMID:10594562

  8. Isolation of antioxidative phenolic glucosides from lemon juice and their suppressive effect on the expression of blood adhesion molecules.

    PubMed

    Miyake, Yoshiaki; Mochizuki, Mika; Okada, Miki; Hiramitsu, Masanori; Morimitsu, Yasujiro; Osawa, Toshihiko

    2007-08-01

    Phenolic glucosides having radical scavenging activity were examined from the fraction eluted with 20% methanol on Amberlite XAD-2 resin applied to lemon (Citrus limon) juice by using reversed phase chromatography. Four phenolic glucosides were identified as 1-feruloyl-beta-D-glucopyranoside, 1-sinapoyl-beta-D-glucopyranoside, 6,8-di-C-glucosylapigenin and 6,8-di-C-glucosyldiosmetin by (1)H-NMR, (13)C-NMR, and MS analyses. They exhibited radical scavenging activity for 1,1-diphenyl-2-picrylhydrazyl (DPPH) and superoxide, although the activity was low in comparison with eriocitrin, a potent antioxidant in lemon fruit, and the eriodictyol of its aglycone. The phenolic compounds in lemon juice were examined for their suppressive effect on the expression of blood adhesion molecules by measuring the expression of intercellular adhesion molecule-1 (ICAM-1) in human umbilical vein endothelial cells (HUVECs) induced by necrosis factor-alpha (TNF-alpha). 6,8-Di-C-glucosylapigenin, apigenin, and diosmentin of the flavones were found to significantly suppress the expression of ICAM-1 at 10 muM (P<0.05). The phenolic glucosides isolated in this study were contained in comparative abundance in daidai (Citrus aurantium) and niihime (Citrus unshiu x Citrus tachibana) among the sour citrus juices.

  9. A Chemokine Expressed in Lymphoid High Endothelial Venules Promotes the Adhesion and Chemotaxis of Naive T Lymphocytes

    NASA Astrophysics Data System (ADS)

    Gunn, Michael D.; Tangemann, Kirsten; Tam, Carmen; Cyster, Jason G.; Rosen, Steven D.; Williams, Lewis T.

    1998-01-01

    Preferential homing of naive lymphocytes to secondary lymphoid organs is thought to involve the action of chemokines, yet no chemokine has been shown to have either the expression pattern or the activities required to mediate this process. Here we show that a chemokine represented in the EST database, secondary lymphoid-tissue chemokine (SLC), is expressed in the high endothelial venules of lymph nodes and Peyer's patches, in the T cell areas of spleen, lymph nodes, and Peyer's patches, and in the lymphatic endothelium of multiple organs. SLC is a highly efficacious chemoattractant for lymphocytes with preferential activity toward naive T cells. Moreover, SLC induces firm adhesion of naive T lymphocytes via β 2 integrin binding to the counter receptor, intercellular adhesion molecule-1, a necessary step for lymphocyte recruitment. SLC is the first chemokine demonstrated to have the characteristics required to mediate homing of lymphocytes to secondary lymphoid organs. In addition, the expression of SLC in lymphatic endothelium suggests that the migration of lymphocytes from tissues into efferent lymphatics may be an active process mediated by this molecule.

  10. Drug exposure in a metastatic human lung adenocarcinoma cell line gives rise to cells with differing adhesion, proliferation, and gene expression: Implications for cancer chemotherapy.

    PubMed

    Li, Huiling; He, Jianxing; Zhong, Nanshan; Hoffman, Robert M

    2015-09-01

    The Am1010 cell line was previously established from a metastatic deposit in an arm muscle from a patient with lung adenocarcinoma who had undergone four cycles of chemotherapy with cisplatin and taxol. Am1010 cells were labeled with red fluorescent protein or green fluorescent protein. A total of eight sublines were isolated following in vitro exposure to cisplatin or taxol. The sublines differed with regard to their adhesion and proliferation properties, with certain sublines exhibiting an increased proliferation rate and/or decreased surface adhesion. Gene expression assays demonstrated that tenascin C; cyclin D1; collagen, type 1, α2; integrin α1; related RAS viral (r‑ras) oncogene homolog 2; platelet‑derived growth factor C; and Src homolog 2 domain containing in the focal adhesion pathway, and intercellular adhesion molecule 1, F11 receptor, claudin 7 and cadherin 1 in the cell adhesion pathway, varied in expression among the sublines. The results of the present study suggested that drug exposure may alter the aggressiveness and metastatic potential of cancer cells, which has important implications for cancer chemotherapy.

  11. Expression of kidney injury molecule-1 (Kim-1) in relation to necrosis and apoptosis during the early stages of Cd-induced proximal tubule injury

    SciTech Connect

    Prozialeck, Walter C. Edwards, Joshua R.; Lamar, Peter C.; Liu, Jie; Vaidya, Vishal S.; Bonventre, Joseph V.

    2009-08-01

    Cadmium (Cd) is a nephrotoxic industrial and environmental pollutant that causes a generalized dysfunction of the proximal tubule. Kim-1 is a transmembrane glycoprotein that is normally not detectable in non-injured kidney, but is up-regulated and shed into the urine during the early stages of Cd-induced proximal tubule injury. The objective of the present study was to examine the relationship between the Cd-induced increase in Kim-1 expression and the onset of necrotic and apoptotic cell death in the proximal tubule. Adult male Sprague-Dawley rats were treated with 0.6 mg (5.36 {mu}mol) Cd/kg, subcutaneously, 5 days per week for up to 12 weeks. Urine samples were analyzed for levels of Kim-1 and the enzymatic markers of cell death, lactate dehydrogenase (LDH) and alpha-glutathione-S-transferase ({alpha}-GST). In addition, necrotic cells were specifically labeled by perfusing the kidneys in situ with ethidium homodimer using a procedure that has been recently developed and validated in the Prozialeck laboratory. Cryosections of the kidneys were also processed for the immunofluorescent visualization of Kim-1 and the identification of apoptotic cells by TUNEL labeling. Results showed that significant levels of Kim-1 began to appear in the urine after 6 weeks of Cd treatment, whereas the levels of total protein, {alpha}-GST and LDH were not increased until 8-12 weeks. Results of immunofluorescence labeling studies showed that after 6 weeks and 12 weeks, Kim-1 was expressed in the epithelial cells of the proximal tubule, but that there was no increase in the number of necrotic cells, and only a modest increase in the number of apoptotic cells at 12 weeks. These results indicate that the Cd-induced increase in Kim-1 expression occurs before the onset of necrosis and at a point where there is only a modest level of apoptosis in the proximal tubule.

  12. Expression of kidney injury molecule-1 (Kim-1) in relation to necrosis and apoptosis during the early stages of Cd-induced proximal tubule injury

    PubMed Central

    Prozialeck, Walter C.; Edwards, Joshua R.; Lamar, Peter C.; Liu, Jie; Vaidya, Vishal S.; Bonventre, Joseph V.

    2009-01-01

    Cadmium (Cd) is a nephrotoxic industrial and environmental pollutant that causes a generalized dysfunction of the proximal tubule. Kim-1 is a transmembrane glycoprotein that is normally not detectable in non-injured kidney, but is up-regulated and shed into the urine during the early stages of Cd-induced proximal tubule injury. The objective of the present study was to examine the relationship between the Cd-induced increase in Kim-1 expression and the onset of necrotic and apoptotic cell death in the proximal tubule. Adult male Sprague-Dawley rats were treated with 0.6 mg (5.36 μmoles) Cd/kg, subcutaneously, 5 days per week for up to 12 weeks. Urine samples were analyzed for levels of Kim-1 and the enzymatic markers of cell death, lactate dehydrogenase (LDH) and alpha-glutathione-S-transferase (α-GST). In addition, necrotic cells were specifically labeled by perfusing the kidneys in situ with ethidium homodimer using a procedure that has been recently developed and validated in the Prozialeck laboratory. Cryosections of the kidneys were also processed for the immunofluorescent visualization of Kim-1 and the identification of apoptotic cells by TUNEL labeling. Results showed that significant levels of Kim-1 began to appear in the urine after 6 weeks of Cd treatment, whereas the levels of total protein, α-GST and LDH were not increased until 8–12 weeks. Results of immunofluorescence labeling studies showed that after 6 weeks and 12 weeks, Kim-1 was expressed in the epithelial cells of the proximal tubule, but that there was no increase in the number of necrotic cells, and only a modest increase in the number of apoptotic cells at 12 weeks. These results indicate that the Cd-induced increase in Kim-1 expression occurs before the onset of necrosis and at a point where there is only a modest level of apoptosis in the proximal tubule. PMID:19371613

  13. TNF-α increases endothelial progenitor cell adhesion to the endothelium by increasing bond expression and affinity

    PubMed Central

    Prisco, Anthony R.; Prisco, Michael R.; Carlson, Brian E.

    2014-01-01

    Endothelial progenitor cells (EPCs) are a rare population of cells that participate in angiogenesis. To effectively use EPCs for regenerative therapy, the mechanisms by which they participate in tissue repair must be elucidated. This study focused on the process by which activated EPCs bind to a target tissue. It has been demonstrated that EPCs can bind to endothelial cells (ECs) through the tumore necrosis factor-α (TNF-α)-regulated vascular cell adhesion molecule 1/very-late antigen 4 (VLA4) interaction. VLA4 can bind in a high or low affinity state, a process that is difficult to experimentally isolate from bond expression upregulation. To separate these processes, a new parallel plate flow chamber was built, a detachment assay was developed, and a mathematical model was created that was designed to analyze the detachment assay results. The mathematical model was developed to predict the relative expression of EPC/EC bonds made for a given bond affinity distribution. EPCs treated with TNF-α/vehicle were allowed to bind to TNF-α/vehicle-treated ECs in vitro. Bound cells were subjected to laminar flow, and the cellular adherence was quantified as a function of shear stress. Experimental data were fit to the mathematical model using changes in bond expression or affinity as the only free parameter. It was found that TNF-α treatment of ECs increased adhesion through bond upregulation, whereas TNF-α treatment of EPCs increased adhesion by increasing bond affinity. These data suggest that injured tissue could potentially increase recruitment of EPCs for tissue regeneration via the secretion of TNF-α. PMID:25539711

  14. BLOOD LEUKOCYTE EXPRESSION OF LFA-1 AND INTRACELLULAR ADHESION MOLECULE-1 (ICAM-1) AFTER INHALATION OF ULTRAFINE CARBON PARTICLES. (R827354C003)

    EPA Science Inventory

    The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

  15. ROCK inhibitor fasudil attenuated high glucose-induced MCP-1 and VCAM-1 expression and monocyte-endothelial cell adhesion.

    PubMed

    Li, Hailing; Peng, Wenhui; Jian, Weixia; Li, Yuanmin; Li, Qi; Li, Weiming; Xu, Yawei

    2012-06-13

    Previous studies suggested that the RhoA/ROCK pathway may contribute to vascular complications in diabetes. The present study was designed to investigate whether ROCK inhibitor fasudil could prevent high glucose-induced monocyte-endothelial cells adhesion, and whether this was related to fasudil effects on vascular endothelial cell expression of chemotactic factors, vascular cell adhesion molecule-1 (VCAM-1) and monocyte chemoattractant protein-1 (MCP-1). HUVECs were stimulated with high glucose (HG) or HG + fasudil in different concentration or different time. Monocyte-endothelial cell adhesion was determined using fluorescence-labeled monocytes. The mRNA and protein expression of VCAM-1 and MCP-1 were measured using real-time PCR and western blot. The protein levels of RhoA, ROCKI and p-MYPT were determined using western blot analysis. ELISA was employed to measure the expression of soluble VCAM-1 and MCP-1 in cell supernatants and human serum samples. Fasudil significantly suppressed HG-induced adhesion of THP-1 to HUVECs. Fasudil reduced Rho/ROCK activity (as indicated by lower p-MYPT/MYPT ratio), and prevented HG induced increases in VCAM-1 and MCP-1 mRNA and protein levels. Fasudil also decreased MCP-1 concentration in HUVEC supernatants, but increased sVCAM-1 shedding into the media. In human diabetic subjects, 2 weeks of fasudil treatment significantly decreased serum MCP-1 level from 27.9 ± 10.6 pg/ml to 13.8 ± 7.0 pg/ml (P < 0.05), while sVCAM-1 increased from 23.2 ± 7.5 ng/ml to 39.7 ± 5.6 ng/ml after fasudil treatment (P < 0.05). Treatment with the Rho/ROCK pathway inhibitor fasudil attenuated HG-induced monocyte-endothelial cell adhesion, possibly by reducing endothelial expression of VCAM-1 and MCP-1. These results suggest inhibition of Rho/ROCK signaling may have therapeutic potential in preventing diabetes associated vascular inflammation and atherogenesis.

  16. Improved adhesive properties of recombinant bifidobacteria expressing the Bifidobacterium bifidum-specific lipoprotein BopA

    PubMed Central

    2012-01-01

    Background Bifidobacteria belong to one of the predominant bacterial groups in the intestinal microbiota of infants and adults. Several beneficial effects on the health status of their human hosts have been demonstrated making bifidobacteria interesting candidates for probiotic applications. Adhesion of probiotics to the intestinal epithelium is discussed as a prerequisite for colonisation of and persistence in the gastrointestinal tract. Results In the present study, 15 different strains of bifidobacteria were tested for adhesion. B. bifidum was identified as the species showing highest adhesion to all tested intestinal epithelial cell (IEC) lines. Adhesion of B. bifidum S17 to IECs was strongly reduced after treatment of bacteria with pronase. These results strongly indicate that a proteinaceous cell surface component mediates adhesion of B. bifidum S17 to IECs. In silico analysis of the currently accessible Bifidobacterium genomes identified bopA encoding a lipoprotein as a B. bifidum-specific gene previously shown to function as an adhesin of B. bifidum MIMBb75. The in silico results were confirmed by Southern Blot analysis. Furthermore, Northern Blot analysis demonstrated that bopA is expressed in all B. bifidum strains tested under conditions used to cultivate bacteria for adhesion assays. The BopA gene was successfully expressed in E. coli and purified by Ni-NTA affinity chromatography as a C-terminal His6-fusion. Purified BopA had an inhibitory effect on adhesion of B. bifidum S17 to IECs. Moreover, bopA was successfully expressed in B. bifidum S17 and B. longum/infantis E18. Strains overexpressing bopA showed enhanced adhesion to IECs, clearly demonstrating a role of BopA in adhesion of B. bifidum strains. Conclusions BopA was identified as a B. bifidum-specific protein involved in adhesion to IECs. Bifidobacterium strains expressing bopA show enhanced adhesion. Our results represent the first report on recombinant bifidobacteria with improved adhesive

  17. Ramalin inhibits VCAM-1 expression and adhesion of monocyte to vascular smooth muscle cells through MAPK and PADI4-dependent NF-kB and AP-1 pathways.

    PubMed

    Park, Bongkyun; Yim, Joung-Han; Lee, Hong-Kum; Kim, Byung-Oh; Pyo, Suhkneung

    2015-01-01

    Cell adhesion molecules play a critical role in inflammatory processes and atherosclerosis. In this study, we investigated the effect of ramalin, a chemical compound from the Antarctic lichen Ramalina terebrata, on vascular cell adhesion molecule-1 (VCAM-1) expression induced by TNF-α in vascular smooth muscular cells (VSMCs). Pretreatment of VSMCs with ramalin (0.1-10 μg/mL) concentration-dependently inhibited TNF-α-induced VCAM-1 expression. Additionally, ramalin inhibited THP-1 (human acute monocytic leukemia cell line) cell adhesion to TNF-α-stimulated VSMCs. Ramalin suppressed TNF-α-induced production of reactive oxygen species (ROS), PADI4 expression, and phosphorylation of p38, ERK, and JNK. Moreover, ramalin inhibited TNF-α-induced translocation of NF-κB and AP-1. Inhibition of PADI4 expression by small interfering RNA or the PADI4-specific inhibitor markedly attenuated TNF-α-induced activation of NF-κB and AP-1 and VCAM-1 expression in VSMCs. Our study provides insight into the mechanisms underlying ramalin activity and suggests that ramalin may be a potential therapeutic agent to modulate inflammation within atherosclerosis.

  18. Raf Kinase Inhibitor Protein (RKIP) Inhibits Tumor Necrosis Factor-α (TNF-α) Induced Adhesion Molecules Expression in Vascular Smooth Muscle Bells by Suppressing (Nuclear Transcription Factor-κB (NF-kappaB) Pathway.

    PubMed

    Jing, Shen-Hong; Gao, Xuan; Yu, Bo; Qiao, Hong

    2017-10-06

    BACKGROUND Raf kinase inhibitor protein (RKIP) regulates growth and differentiation and plays a role in key signal transduction cascades in mammalian cells. Nevertheless, the underlying mechanism for which RKIP regulates cell-cell adhesion remains unknown. Our study investigated the function of the RKIP overexpression on adhesion molecules expression induced by tumor necrosis factor (TNF)-α in cultured mouse vascular smooth muscle cells (MOVACs). MATERIAL AND METHODS The expression levels of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) were detected by ELISA kit, reverse transcription-PCR, and western blot assays. The protein expression of RKIP, p65, and inhibitor of nuclear factor (NF)-κBα (IκBα) were detected by western blot analysis. The activity of NF-kappaB was determined using a Dual-Luciferase Reporter assay. RESULTS The results showed that MOVACs transfected with pCMV5-HA-RKIP significantly inhibited TNF-α induced mRNA and protein expression of ICAM-1 and VCAM-1. The adhesion of THP-1 cells was also detected and inhibited by pCMV5-HA-RKIP in TNF-α-treated MOVACs. RKIP also suppressed the TNF-α-induced activation of NF-kappaB and the protein expression of phosphorylated IκB-α, and promoted the protein expression of IkB-α and nuclear translocation of p65 NF-kappaB. Furthermore, RKIP and the inhibitor of NF-kappaB (BAY11-7082) reduced the upregulation of ICAM-1 and VACM-1 induced by TNF-α. CONCLUSIONS Taken together, these results suggested that RKIP may inhibit the TNF-α-induced expression of adhesion molecules in MOVACs through inactivation of the NF-kappaB pathway.

  19. Role of glucocorticoids in neutrophil and endothelial adhesion molecule expression and function

    PubMed Central

    Talbot, Vivienne

    1992-01-01

    Glucocorticoids are very effective inhibitors of both the acute and chronic inflammatory response. In this study the hypothesis that glucocorticoids inhibit an early component of the inflammatory response, neutrophil adhesion to endothelium, by down-regulation of adhesion molecules on neutrophils or endothelium was examined. No effect of dexamethasone on neutrophil adhesion to endothelium or of antigen expression by neutrophils or endothelium was found. The mechanism of action of glucocorticoids in the inflammatory response is probably not mediated by alterations in adhesion molecules. PMID:18475448

  20. Transglutaminase 2 expression in acute myeloid leukemia: Association with adhesion molecule expression and leukemic blast motility

    PubMed Central

    Meyer, Stefan; Ravandi-Kashani, Farhad; Borthakur, Gautam; Coombes, Kevin R.; Zhang, Nianxiang; Kornblau, Steven

    2016-01-01

    Acute myeloid leukemia (AML) is a heterogenous disease with differential oncogene association, outcome and treatment regimens. Treatment strategies for AML have improved outcome but despite increased molecular biological information AML is still associated with poor prognosis. Proteomic analysis on the effects of a range of leukemogenic oncogenes showed that the protein transglutaminase 2 (TG2) is expressed at greater levels as a consequence of oncogenic transformation. Further analysis of this observation was performed with 511 AML samples using reverse phase proteomic arrays, demonstrating that TG2 expression was higher at relapse than diagnosis in many cases. In addition elevated TG2 expression correlated with increased expression of numerous adhesion proteins and many apoptosis regulating proteins, two processes related to leukemogenesis. TG2 has previously been linked to drug resistance in cancer and given the negative correlation between TG2 levels and peripheral blasts observed increased TG2 levels may lead to the protection of the leukemic stem cell due to increased adhesion/reduced motility. TG2 may therefore form part of a network of proteins that define poor outcome in AML patients and potentially offer a target to sensitize AML stem cells to drug treatment. PMID:23576428

  1. Glycated LDL increase VCAM-1 expression and secretion in endothelial cells and promote monocyte adhesion through mechanisms involving endoplasmic reticulum stress.

    PubMed

    Toma, Laura; Sanda, Gabriela M; Deleanu, Mariana; Stancu, Camelia S; Sima, Anca V

    2016-06-01

    Type 2 Diabetes Mellitus is a worldwide epidemic, and its atherosclerotic complications produce morbidity and mortality in affected patients. It is known that the vascular cell adhesion molecule-1 (VCAM-1) levels are increased in the sera of diabetic patients. Our aim was to investigate the impact of the endoplasmic reticulum stress (ERS) in VCAM-1 expression and secretion in human endothelial cells (HEC) exposed to glycated low-density lipoproteins (gLDL). The results showed that 24 h incubation of HEC with gLDL induces (i) stimulation of VCAM-1 expression and secretion, determining increased monocyte adhesion to HEC; (ii) RAGE up-regulation and free cholesterol loading; (iii) ERS activation (increased eIF2α phosphorylation and CHOP mRNA levels, and decreased GRP78 protein expression); and (iv) oxidative stress [increased levels of reactive oxygen species (ROS) and glutamate cysteine ligase catalytic unit gene expression]. Treatment of gLDL-exposed HEC with ERS inhibitors, salubrinal (Sal) and sodium phenylbutyrate (PBA), decreased intracellular ROS. Incubation of gLDL-exposed cells with the anti-oxidant N-acetyl-cysteine (NAC) reduced ERS, revealed by decreased eIF2α phosphorylation and CHOP gene expression and increased GRP78 expression, thus validating the interconnection between ERS and oxidative stress. Sal, PBA, NAC and inhibitors of p38 MAP kinase and NF-kB induced the decrease of VCAM-1 expression and of the ensuing monocyte adhesion induced by gLDL. In conclusion, in HEC, gLDL stimulate the expression of cellular VCAM-1, the secretion of soluble VCAM-1, and the adhesion of monocytes through mechanisms involving p38 MAP kinase and NF-kB signalling pathways activated by RAGE, ERS and oxidative stress, thus contributing to diabetic atherosclerosis.

  2. Noradrenaline reuptake inhibitors inhibit expression of chemokines IP-10 and RANTES and cell adhesion molecules VCAM-1 and ICAM-1 in the CNS following a systemic inflammatory challenge.

    PubMed

    O'Sullivan, Joan B; Ryan, Karen M; Harkin, Andrew; Connor, Thomas J

    2010-03-30

    Evidence suggests that noradrenaline has a tonic anti-inflammatory action in the central nervous system (CNS) via its ability to inhibit expression of inflammatory mediators from glial cells. Consequently it is suggested that noradrenaline may play an endogenous neuroprotective role in CNS disorders where inflammatory events contribute to pathology. Infiltration of peripheral immune cells into the brain is driven by increased chemokine and cell adhesion molecule (CAM) expression, and is known to exacerbate neuroinflammation and thereby contribute to the disease process in a number of neurodegenerative disease states. Here we demonstrate that treatment of rats with the noradrenaline reuptake inhibitors (NRIs) desipramine and atomoxetine, agents that increase extracellular noradrenaline in the CNS, suppressed chemokine and cell adhesion molecule (CAM) expression in rat brain following a systemic challenge with bacterial lipopolysaccharide (LPS). Specifically, these agents reduced expression of the chemokines, interferon-inducible protein-10 (IP-10, CXCL-10) and regulated upon activation normal T-cell expressed and secreted (RANTES, CCL-5), and the CAMs, vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule (ICAM-1) in cortex and hippocampus. The inhibitory action of NRIs on chemokines and CAM expression was mimicked by in vitro exposure of cultured glial cells to noradrenaline, but not to the NRIs themselves. These data indicate that the suppressive action of NRIs on chemokine and CAM expression that occurs in vivo is due to increased noradrenaline availability at glial cells, as opposed to a direct action of the drugs on glial cells per se. These results support the theory that noradrenaline has anti-inflammatory properties, and agents that increase noradrenaline availability in vivo can play a role in combating brain inflammation by reducing expression of chemokines and CAMs; molecules that facilitate leucocyte influx into the CNS

  3. Proinflammatory Cytokine, Chemokine, and Cellular Adhesion Molecule Expression during the Acute Phase of Experimental Brain Abscess Development

    PubMed Central

    Kielian, Tammy; Hickey, William F.

    2000-01-01

    Brain abscess represents the infectious disease sequelae associated with the influx of inflammatory cells and activation of resident parenchymal cells in the central nervous system. However, the immune response leading to the establishment of a brain abscess remains poorly defined. In this study, we have characterized cytokine and chemokine expression in an experimental brain abscess model in the rat during the acute stage of abscess development. RNase protection assay revealed the induction of the proinflammatory cytokines interleukin (IL)-1α, IL-1β, IL-6, and tumor necrosis factor-α as early as 1 to 6 hours after Staphylococcus aureus exposure. Evaluation of chemokine expression by reverse transcription-polymerase chain reaction demonstrated enhanced levels of the CXC chemokine KC 24 hours after bacterial exposure, which correlated with the appearance of neutrophils in the abscess. In addition, two CC chemokines, monocyte chemoattractant protein-1 and macrophage inflammatory protein-1α were induced within 24 hours after S. aureus exposure and preceded the influx of macrophages and lymphocytes into the brain. Analysis of abscess lesions by in situ hybridization identified CD11b+ cells as the source of IL-1β in response to S. aureus. Both intercellular adhesion molecule-1 and platelet endothelial cell adhesion molecule expression were enhanced on microvessels in S. aureus but not sterile bead-implanted tissues at 24 and 48 hours after treatment. These results characterize proinflammatory cytokine and chemokine expression during the early response to S. aureus in the brain and provide the foundation to assess the functional significance of these mediators in brain abscess pathogenesis. PMID:10934167

  4. Dietary Selenium Supplementation Modulates Growth of Brain Metastatic Tumors and Changes the Expression of Adhesion Molecules in Brain Microvessels.

    PubMed

    Wrobel, Jagoda K; Wolff, Gretchen; Xiao, Rijin; Power, Ronan F; Toborek, Michal

    2016-08-01

    Various dietary agents can modulate tumor invasiveness. The current study explored whether selenoglycoproteins (SeGPs) extracted from selenium-enriched yeast affect tumor cell homing and growth in the brain. Mice were fed diets enriched with specific SeGPs (SeGP40 or SeGP65, 1 mg/kg Se each), glycoproteins (GP40 or GP65, 0.2-0.3 mg/kg Se each) or a control diet (0.2-0.3 mg/kg Se) for 12 weeks. Then, murine Lewis lung carcinoma cells were infused into the brain circulation. Analyses were performed at early (48 h) and late stages (3 weeks) post tumor cell infusion. Imaging of tumor progression in the brain revealed that mice fed SeGP65-enriched diet displayed diminished metastatic tumor growth, fewer extravasating tumor cells and smaller metastatic lesions. While administration of tumor cells resulted in a significant upregulation of adhesion molecules in the early stage of tumor progression, overexpression of VCAM-1 (vascular call adhesion molecule-1) and ALCAM (activated leukocyte cell adhesion molecule) messenger RNA (mRNA) was diminished in SeGP65 supplemented mice. Additionally, mice fed SeGP65 showed decreased expression of acetylated NF-κB p65, 48 h post tumor cell infusion. The results indicate that tumor progression in the brain can be modulated by specific SeGPs. Selenium-containing compounds were more effective than their glycoprotein controls, implicating selenium as a potential negative regulator of metastatic process.

  5. Endothelial tetraspanin microdomains regulate leukocyte firm adhesion during extravasation.

    PubMed

    Barreiro, Olga; Yáñez-Mó, María; Sala-Valdés, Mónica; Gutiérrez-López, María Dolores; Ovalle, Susana; Higginbottom, Adrian; Monk, Peter N; Cabañas, Carlos; Sánchez-Madrid, Francisco

    2005-04-01

    Tetraspanins associate with several transmembrane proteins forming microdomains involved in intercellular adhesion and migration. Here, we show that endothelial tetraspanins relocalize to the contact site with transmigrating leukocytes and associate laterally with both intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). Alteration of endothelial tetraspanin microdomains by CD9-large extracellular loop (LEL)-glutathione S-transferase (GST) peptides or CD9/CD151 siRNA oligonucleotides interfered with ICAM-1 and VCAM-1 function, preventing lymphocyte transendothelial migration and increasing lymphocyte detachment under shear flow. Heterotypic intercellular adhesion mediated by VCAM-1 or ICAM-1 was augmented when expressed exogenously in the appropriate tetraspanin environment. Therefore, tetraspanin microdomains have a crucial role in the proper adhesive function of ICAM-1 and VCAM-1 during leukocyte adhesion and transendothelial migration.

  6. Human Immunodeficiency Virus (HIV) Type 1 Vpu Induces the Expression of CD40 in Endothelial Cells and Regulates HIV-Induced Adhesion of B-Lymphoma Cells

    PubMed Central

    Henderson, Winnie W.; Ruhl, Rebecca; Lewis, Paul; Bentley, Matthew; Nelson, Jay A.; Moses, Ashlee V.

    2004-01-01

    AIDS-related B-cell non-Hodgkin's lymphoma (AIDS-NHL) is a significant cause of morbidity and mortality among individuals infected with human immunodeficiency virus type 1 (HIV-1). AIDS-NHL is clinically and histologically heterogeneous, but common features include an aggressive clinical course and frequent extranodal presentation. HIV-1 infection of nonimmune cells that interact with malignant B cells at extranodal sites may influence both the development and the clinical presentation of disease. Our previous studies have shown that coculture of B-lymphoma (BL) cells with HIV-1-infected endothelial cells (EC) leads to contact activation of EC and firm BL-cell adhesion. The key event promoting EC-BL-cell adhesion was HIV-1 upregulation of endothelial CD40, which allowed induction of vascular cell adhesion molecule 1 (VCAM-1) in a CD40-dependent manner. The present study was designed to identify the HIV-1 protein(s) that influence EC-BL-cell adhesion. When HIV-1 proteins were individually expressed in EC by using recombinant adenoviruses, cultured BL cells adhered exclusively to Vpu-transduced EC. As with HIV-infected EC, adhesive properties were linked to the capacity of Vpu to upregulate CD40, which in turn allowed efficient expression of VCAM-1. When EC were infected with an HIV-1 pseudotype lacking the Vpu gene, CD40 upregulation and BL-cell adhesive properties were lost, indicating an essential role for Vpu in EC-BL-cell interactions. Thus, these data reveal a novel function for HIV-1 Vpu and further suggest a role for Vpu in the development of AIDS-NHL at EC-rich extranodal sites. PMID:15078922

  7. Sodium chloride affects Listeria monocytogenes adhesion to polystyrene and stainless steel by regulating flagella expression.

    PubMed

    Caly, D; Takilt, D; Lebret, V; Tresse, O

    2009-12-01

    To study the adhesion capability of seven strains of Listeria monocytogenes to polystyrene and stainless steel surfaces after cultivation at various NaCl concentrations. Determination of growth limits indicated that all seven strains were able to grow in up to 11% NaCl in rain heart infusion and 3 g l(-1) yeast extract-glucose at 20 degrees C, but no growth was detected at 15% NaCl. Adhesion of L. monocytogenes was estimated after 4-h incubation at 20 degrees C in 96-well microtitre plates. Statistical results revealed no significant difference between adhesion to polystyrene and stainless steel although surface properties were different. Adhesion between 0% and 6% NaCl was not different, whereas adhesion at 11% NaCl was significantly lower. This discrepancy in adhesion was correlated with the down-regulation of flagella at 11% NaCl. Only high salinity levels, close to nongrowth conditions, repressed the expression of flagella, and consequently, decreased the adhesion capability of L. monocytogenes. Adhesion of L. monocytogenes to inert surfaces depends on environmental conditions that affect flagellum expression. High salinity concentrations would delay biofilm formation.

  8. Macrophage function in alloxan diabetic mice: expression of adhesion molecules, generation of monokines and oxygen and NO radicals

    PubMed Central

    Ptak, W; Klimek, M; Bryniarski, K; Ptak, M; Majcher, P

    1998-01-01

    The increased incidence of bacterial and mycotic infections in poorly controlled diabetic patients or animals is frequently attributed to impaired activities of professional phagocytes (granulocytes, macrophages) in hypoinsulinaemic milieu. We measured production of monokines (IL-6 and tumour necrosis factor-alpha (TNF-α)), active NO and reactive oxygen intermediates (ROIs), as well as expression of several cell surface adhesion molecules (Mac-1, -2 and -3, intercellular adhesion molecule-1 (ICAM-1) and FcγRII), by thioglycollate medium-induced peritoneal macrophages of normoglycaemic and alloxan diabetic CBA/J mice (blood glucose level in the range 300 or 500 mg/dl). Macrophages of animals with moderate diabetes (300 mg/dl) produced significantly more IL-6 and TNF-α and ROIs than cells of control mice and showed an increased expression of all cell surface molecules, except Mac-3. NO/NO2 production was not affected. Administration of insulin restored enhanced values to normal levels, except for the production of ROIs which remained unusually high. We conclude that two separate mechanisms influence macrophage physiology in diabetes—lack of saturation of insulin receptors on macrophages and an indirect effect due to formation of advanced glycosylation endproducts (AGE) on their surfaces. The latter is possibly responsible for increased generation of ROIs, since it cannot be down-regulated by prolonged insulin treatment. How the increased activity of macrophages of moderately diabetic mice (enhanced production of proinflammatory monokines and oxygen radicals as well as expression of molecules) is related to their ability to kill bacteria is now under investigation. PMID:9764597

  9. PM2.5-induced oxidative stress increases adhesion molecules expression in human endothelial cells through the ERK/AKT/NF-κB-dependent pathway.

    PubMed

    Rui, Wei; Guan, Longfei; Zhang, Fang; Zhang, Wei; Ding, Wenjun

    2016-01-01

    The aim of this study was to explore the intracellular mechanisms underlying the cardiovascular toxicity of air particulate matter (PM) with an aerodynamic diameter of less than 2.5 µm (PM2.5) in a human umbilical vein cell line, EA.hy926. We found that PM2.5 exposure triggered reactive oxygen species (ROS) generation, resulting in a significant decrease in cell viability. Data from Western blots showed that PM2.5 induced phosphorylation of Jun N-terminal kinase (JNK), extracellular signal regulatory kinase (ERK), p38 mitogen-activated protein kinase (MAPK) and protein kinase B (AKT), and activation of nuclear factor kappa B (NF-κB). We further observed a significant increase in expressions of intercellular adhesion molecule-1 (ICAM-1) and vascular adhesion molecule-1 (VCAM-1) in a time- and dose-dependent manner. Moreover, the adhesion of monocytic THP-1 cells to EA.hy926 cells was greatly enhanced in the presence of PM2.5 . However, N-acetylcysteine (NAC), a scavenger of ROS, prevented the increase of ROS generation, attenuated the phosphorylation of the above kinases, and decreased the NF-κB activation as well as the expression of ICAM-1 and VCAM-1. Furthermore, ERK inhibitor (U0126), AKT inhibitor (LY294002) and NF-κB inhibitor (BAY11-7082) significantly down-regulated PM2.5 -induced ICAM-1 and VCAM-1 expression as well as adhesion of THP-1 cells, but not JNK inhibitor (SP600125) and p38 MAPK inhibitor (SB203580), indicating that ERK/AKT/NF-κB is involved in the signaling pathway that leads to PM2.5 -induced ICAM-1 and VCAM-1 expression. These findings suggest PM2.5 -induced ROS may function as signaling molecules triggering ICAM-1 and VCAM-1 expressions through activating the ERK/AKT/NF-κB-dependent pathway, and further promoting monocyte adhesion to endothelial cells.

  10. Kidney injury molecule-1 in kidney disease.

    PubMed

    Yin, Caixia; Wang, Ningning

    2016-11-01

    Kidney injury molecule-1(KIM-1) is a type I membrane protein, comprising an extracellular portion and a cytoplasmic portion, which is expressed at very low levels in the normal kidney. The extracellular portion can cleave and rapidly enter tubule lumens after kidney injury, and can then be detected in the urine. It has been confirmed that the urine KIM-1 level is closely related to tissue KIM-1 level and correlated with kidney tissue damage. Not only is KIM-1 proven to be an early biomarker of acute kidney injury but it also has a potential role in predicting long-term renal outcome. This review summarizes the relationships between KIM-1 and kidney injury, especially in chronic kidney disease.

  11. Elevated expression in situ of selectin and immunoglobulin superfamily type adhesion molecules in retroocular connective tissues from patients with Graves' ophthalmopathy.

    PubMed Central

    Heufelder, A E; Bahn, R S

    1993-01-01

    Activation of certain adhesion molecules within vascular endothelium and the surrounding extravascular space is a critical event in the recruitment and targeting of an inflammatory response or autoimmune attack to a particular tissue site. We have recently demonstrated that the adhesion of lymphocytes to cultured retroocular fibroblasts obtained from patients with Graves' ophthalmopathy (GO) is mediated predominantly by the interaction of lymphocyte function-associated antigen-1 (LFA-1), expressed on lymphocytes, with intercellular adhesion molecule-1 (ICAM-1), expressed by these cells following exposure to interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha), IL-1 alpha or purified thyroid-stimulating immunoglobulins. We now report the expression and localization in situ of several adhesion molecules, ICAM-1, endothelial leucocyte adhesion molecule-1 (ELAM-1), vascular cell adhesion molecule-1 (VCAM-1), and LFA-3 in retroocular tissues derived from patients with severe GO (n = 4) and normal individuals (n = 3). Serial cryostat sections of tissue specimens were processed for immunoperoxidase staining using various MoAbs against ICAM-1, ELAM-1, VCAM-1 and LFA-3. In addition, consecutive sections were stained with MoAbs against LFA-1, CD45RO (UCHL-1)DR-human leucocyte antigen (HLA-DR), CD11b/CD18 (Mac-1), and CD11c/CD18 (p150,95). In GO-retroocular tissues, strong immunoreactivity for ICAM-1 and LFA-3 was detected in blood vessels (> 90%), in perimysial fibroblasts surrounding extraocular muscle fibres, and in connective tissue distinct from extraocular muscle. No ICAM-1 or LFA-3 immunoreactivity was present in extraocular muscle cells themselves. ICAM-1 and LFA-3 immunoreactivity in normal tissues was minimal or absent both in connective and muscle tissues. Vascular endothelium was strongly positive for ELAM-1 and VCAM-1 in GO-retroocular tissues, while VCAM-1 immunoreactivity was minimal (< 5% of blood vessels) and ELAM-1 immunoreactivity was

  12. Hypothermia Increases Tissue Plasminogen Activator Expression and Decreases Post-Operative Intra-Abdominal Adhesion

    PubMed Central

    Lee, Chien-Chang; Wang, Hsuan-Mao; Chou, Tzung-Hsin; Wu, Meng-Che; Hsueh, Kuang-Lung; Chen, Shyr-Chyr

    2016-01-01

    Background Therapeutic hypothermia during operation decreases postoperative intra-abdominal adhesion formation. We sought to determine the most appropriate duration of hypothermia, and whether hypothermia affects the expression of tissue plasminogen activator (tPA). Methods 80 male BALB/c mice weighing 25–30 g are randomized into one of five groups: adhesion model with infusion of 15°C saline for 15 minutes (A); 30 minutes (B); 45 minute (C); adhesion model without infusion of cold saline (D); and sham operation without infusion of cold saline (E). Adhesion scores and tPA levels in the peritoneum fluid levels were analyzed on postoperative days 1, 7, and 14. Results On day 14, the cold saline infusion groups (A, B, and C) had lower adhesion scores than the without infusion of cold saline group (D). However, only group B (cold saline infusion for 30 minutes) had a significantly lower adhesion scores than group D. Also, group B was found to have 3.4 fold, 2.3 fold, and 2.2 fold higher levels of tPA than group D on days 1, 7, and 14 respectively. Conclusions Our results suggest that cold saline infusion for 30 minutes was the optimum duration to decrease postoperative intra-abdominal adhesion formation. The decrease in the adhesion formations could be partly due to an increase in the level of tPA. PMID:27583464

  13. Sulforaphane inhibits TNF-α-induced adhesion molecule expression through the Rho A/ROCK/NF-κB signaling pathway.

    PubMed

    Hung, Chi-Nan; Huang, Hui-Pei; Wang, Chau-Jong; Liu, Kai-Li; Lii, Chong-Kuei

    2014-10-01

    Endothelial dysfunction is an early indicator of cardiovascular diseases. Increased stimulation of tumor necrosis factor-α (TNF-α) triggers the inflammatory mediator secretion of endothelial cells, leading to atherosclerotic risk. In this study, we investigated whether sulforaphane (SFN) affected the expression of intracellular adhesion molecule-1 (ICAM-1) in TNF-α-induced ECV 304 endothelial cells. Our data showed that SFN attenuated TNF-α-induced expression of ICAM-1 in ECV 304 cells. Pretreatment of ECV 304 cells with SFN inhibited dose-dependently the secretion of proinflammatory cytokines, such as interleukin (IL)-1β, IL-6, and IL-8. SFN inhibited TNF-α-induced nuclear factor-κB (NF-κB) DNA binding activity. Furthermore, SFN decreased TNF-α-mediated phosphorylation of IκB kinase (IKK) and IκBα, Rho A, ROCK, ERK1/2, and plasminogen activator inhibitor-1 (PAI-1) levels. Collectively, SFN inhibited the NF-κB DNA binding activity and downregulated the TNF-α-mediated induction of ICAM-1 in endothelial cells by inhibiting the Rho A/ROCK/NF-κB signaling pathway, suggesting the beneficial effects of SFN on suppression of inflammation within the atherosclerotic lesion.

  14. Differential expression of adhesion molecules and chemokines between nasal and small intestinal mucosae: implications for T- and sIgA+ B-lymphocyte recruitment.

    PubMed

    Bourges, Dorothée; Chevaleyre, Claire; Wang, CaiHong; Berri, Mustapha; Zhang, XiaoMei; Nicaise, Laetitia; Meurens, François; Salmon, Henri

    2007-12-01

    Nasal and small intestinal mucosae are the first sites of contact with infectious agents and the sites of T-cell-mediated and secreted immunoglobulin A (IgA)-mediated defences against pathogens. We investigated the factors controlling the infiltration of CD3(+) T lymphocytes and surface IgA(+) (sIgA(+)) B lymphocytes into swine epithelium and lamina propria (LP) within and between these two mucosal effector sites. Vascular addressins, vascular cell adhesion molecule 1 and mucosal addressin cell adhesion molecule-1 were reciprocally expressed in both mucosae. Strong expression of alpha(4)beta(1) relative to alpha(4)beta(7) was characteristic of CD3(+) T cells in nasal mucosa LP and epithelium and of sIgA(+) cells in nasal mucosa epithelium. The same profile was observed on corresponding blood cells. Conversely, higher levels of integrins beta(7) and alpha(4)beta(7) than alpha(4)beta(1) were characteristic of CD3(+) T cells and sIgA(+) cells in the small intestine. However, about 40% of the LP-activated sIgA(+) cells displayed sIgA(high), integrin alpha(4) and integrin alpha(4) expression. Whereas CCL19, CXCL12, CCL21 and CCL28 messenger RNAs were similarly expressed in both mucosae, CCL25 messenger RNA was only expressed in the small intestine. Thus, the nasal and small intestine mucosae represent separate compartments for infiltration by CD3(+) T cells and sIgA(+) effector cells, with the exception of a population of small intestine activated sIgA(+) cells, which may gain access to both mucosae.

  15. Differential expression of adhesion molecules and chemokines between nasal and small intestinal mucosae: implications for T- and sIgA+ B-lymphocyte recruitment

    PubMed Central

    Bourges, Dorothée; Chevaleyre, Claire; Wang, CaiHong; Berri, Mustapha; Zhang, XiaoMei; Nicaise, Laetitia; Meurens, François; Salmon, Henri

    2007-01-01

    Nasal and small intestinal mucosae are the first sites of contact with infectious agents and the sites of T-cell-mediated and secreted immunoglobulin A (IgA)-mediated defences against pathogens. We investigated the factors controlling the infiltration of CD3+ T lymphocytes and surface IgA+ (sIgA+) B lymphocytes into swine epithelium and lamina propria (LP) within and between these two mucosal effector sites. Vascular addressins, vascular cell adhesion molecule 1 and mucosal addressin cell adhesion molecule-1 were reciprocally expressed in both mucosae. Strong expression of α4β1 relative to α4β7 was characteristic of CD3+ T cells in nasal mucosa LP and epithelium and of sIgA+ cells in nasal mucosa epithelium. The same profile was observed on corresponding blood cells. Conversely, higher levels of integrins β7 and α4β7 than α4β1 were characteristic of CD3+ T cells and sIgA+ cells in the small intestine. However, about 40% of the LP-activated sIgA+ cells displayed sIgAhigh, integrin α4 and integrin α4 expression. Whereas CCL19, CXCL12, CCL21 and CCL28 messenger RNAs were similarly expressed in both mucosae, CCL25 messenger RNA was only expressed in the small intestine. Thus, the nasal and small intestine mucosae represent separate compartments for infiltration by CD3+ T cells and sIgA+ effector cells, with the exception of a population of small intestine activated sIgA+ cells, which may gain access to both mucosae. PMID:17635614

  16. Early osteoinductive human bone marrow mesenchymal stromal/stem cells support an enhanced hematopoietic cell expansion with altered chemotaxis- and adhesion-related gene expression profiles.

    PubMed

    Sugino, Noriko; Miura, Yasuo; Yao, Hisayuki; Iwasa, Masaki; Fujishiro, Aya; Fujii, Sumie; Hirai, Hideyo; Takaori-Kondo, Akifumi; Ichinohe, Tatsuo; Maekawa, Taira

    2016-01-22

    Bone marrow (BM) microenvironment has a crucial role in supporting hematopoiesis. Here, by using a microarray analysis, we demonstrate that human BM mesenchymal stromal/stem cells (MSCs) in an early osteoinductive stage (e-MSCs) are characterized by unique hematopoiesis-associated gene expression with an enhanced hematopoiesis-supportive ability. In comparison to BM-MSCs without osteoinductive treatment, gene expression in e-MSCs was significantly altered in terms of their cell adhesion- and chemotaxis-related profiles, as identified with Gene Ontology and Gene Set Enrichment Analysis. Noteworthy, expression of the hematopoiesis-associated molecules CXCL12 and vascular cell adhesion molecule 1 was remarkably decreased in e-MSCs. e-MSCs supported an enhanced expansion of CD34(+) hematopoietic stem and progenitor cells, and generation of myeloid lineage cells in vitro. In addition, short-term osteoinductive treatment favored in vivo hematopoietic recovery in lethally irradiated mice that underwent BM transplantation. e-MSCs exhibited the absence of decreased stemness-associated gene expression, increased osteogenesis-associated gene expression, and apparent mineralization, thus maintaining the ability to differentiate into adipogenic cells. Our findings demonstrate the unique biological characteristics of e-MSCs as hematopoiesis-regulatory stromal cells at differentiation stage between MSCs and osteoprogenitor cells and have significant implications in developing new strategy for using pharmacological osteoinductive treatment to support hematopoiesis in hematopoietic stem and progenitor cell transplantation. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Effects of total flavonoids from Dracocephalum moldavica on the proliferation, migration, and adhesion molecule expression of rat vascular smooth muscle cells induced by TNF-α.

    PubMed

    Xing, Jianguo; Peng, Kejun; Cao, Wenjiang; Lian, Xuhui; Wang, Qiulin; Wang, Xinchun

    2013-01-01

    Dracocephalum moldavica Linn (Labiatae) is one of the ethnomedicinal drugs of Uygur in Xinjiang, China. This herb is mainly used in treating cardiovascular diseases, such as atherosclerosis. However, the mechanism of pharmacological activity of D. moldavica has been poorly studied. To explore the pharmacological mechanism of D. moldavica in treating atherosclerosis by investigating the effects of total flavonoids from the aerial portion of D. moldavica on rat vascular smooth muscle cells (VSMCs). The proliferation and migration of VSMCs were evaluated via a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and transwell chamber experiment, respectively. The expression of proliferating cell nuclear antigen (PCNA), nuclear factor κB p65 (NF-κB p65), intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) of VSMCs was determined using immunohistochemistry staining and quantitative real-time PCR (qRT-PCR). Total flavonoids (IC(50) = 145.63 μg/mL) significantly inhibited tumor necrosis factor-α (TNF-α) induced VSMC proliferation at concentrations of 25, 50, and 100 μg/mL. Treatment with 50 and 100 μg/mL of total flavonoids also significantly inhibited TNF-α-induced VSMC migration, whereas 25 μg/mL of total flavonoids did not elicit any significant inhibitory effect. In addition, the effects of total flavonoids on inflammatory molecule expression of cells were tested by immunohistochemistry staining, showing that TNF-α-induced expression of PCNA, NF-κB p65, ICAM-1, and VCAM-1 in VSMCs was dose-dependently suppressed by total flavonoids. Furthermore, qRT-PCR data confirmed the inhibition of mRNA expressions of these inflammatory molecules. These data suggest that total flavonoids from D. moldavica exhibit anti-inflammatory activities, which is probably one of the underlying mechanisms of D. moldavica for clinical treatment of atherosclerosis.

  18. A hot water extract of Curcuma longa inhibits adhesion molecule protein expression and monocyte adhesion to TNF-α-stimulated human endothelial cells.

    PubMed

    Kawasaki, Kengo; Muroyama, Koutarou; Yamamoto, Norio; Murosaki, Shinji

    2015-01-01

    The recruitment of arterial leukocytes to endothelial cells is an important step in the progression of various inflammatory diseases. Therefore, its modulation is thought to be a prospective target for the prevention or treatment of such diseases. Adhesion molecules on endothelial cells are induced by proinflammatory cytokines, including tumor necrosis factor-α (TNF-α), and contribute to the recruitment of leukocytes. In the present study, we investigated the effect of hot water extract of Curcuma longa (WEC) on the protein expression of adhesion molecules, monocyte adhesion induced by TNF-α in human umbilical vascular endothelial cells (HUVECs). Treatment of HUVECs with WEC significantly suppressed both TNF-α-induced protein expression of adhesion molecules and monocyte adhesion. WEC also suppressed phosphorylation and degradation of nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκBα) induced by TNF-α in HUVECs, suggesting that WEC inhibits the NF-κB signaling pathway.

  19. Therapy with hydroxyurea is associated with reduced adhesion molecule gene and protein expression in sickle red cells with a concomitant reduction in adhesive properties.

    PubMed

    Gambero, Sheley; Canalli, Andreia A; Traina, Fabiola; Albuquerque, Dulcinéia M; Saad, Sara T O; Costa, Fernando F; Conran, Nicola

    2007-02-01

    Propagation of the vaso-occlusive process in sickle cell anaemia (SCA) is a complex process involving the adhesion of steady-state SCA patients red cells and reticulocytes to the vascular endothelium. The effect of hydroxyurea therapy (HUT) on the adhesive properties of sickle cells and the expression of adhesion molecule genes by erythroid cells of SCA individuals is not yet fully understood. The expressions of the CD36 gene and the VLA-4-integrin subunit genes, CD49d (alpha-subunit) and CD29 (beta-subunit), were compared in the reticulocytes of steady-state SCA patients and patients on HUT using real-time PCR. Basal adhesion of red cells from these subjects was also compared using static adhesion assays, as was surface protein expression, using flow cytometry. Basal sickle red cell adhesion to fibronectin was significantly greater than that of normal cells (P < 0.01); in contrast, HUT was associated with significantly lower levels (P < 0.01) of red cell adhesion that were similar to those of control cells; this decrease could not be justified solely by altered reticulocyte numbers in this population. Accordingly, flow cytometry demonstrated that reticulocytes from patients on HUT had significantly lower CD36 and CD49d surface expressions (P < 0.01) and, importantly, significantly lower expressions of the CD36, CD49d and CD29 genes (P < 0.05) than reticulocytes of SCA patients not on HUT. Taken together, data support the hypothesis that HUT reduces the adhesive properties of sickle cells and that this decrease appears to be mediated, at least in part, by a decrease in the gene and, consequently, surface protein expression of adhesion molecules such as VLA-4 and CD36.

  20. Transfection of IL-10 expression vectors into endothelial cultures attenuates α4β7-dependent lymphocyte adhesion mediated by MAdCAM-1

    PubMed Central

    Sasaki, Makoto; Jordan, Paul; Houghton, Jeff; Meng, Xianmin; Itoh, Makoto; Joh, Takashi; Alexander, J Steven

    2003-01-01

    Background Enhanced expression of MAdCAM-1 (mucosal addressin cell adhesion molecule-1) is associated with the onset and progression of inflammatory bowel disease. The clinical significance of elevated MAdCAM-1 expression is supported by studies showing that immunoneutralization of MAdCAM-1, or its ligands reduce inflammation and mucosal damage in models of colitis. Interleukin-10 (IL-10) is an endogenous anti-inflammatory and immunomodulatory cytokine that has been shown to prevent inflammation and injury in several animal studies, however clinical IL-10 treatment remains insufficient because of difficulties in the route of IL-10 administration and its biological half-life. Here, we examined the ability of introducing an IL-10 expression vector into endothelial cultures to reduce responses to a proinflammatory cytokine, TNF-α Methods A human IL-10 expression vector was transfected into high endothelial venular ('HEV') cells (SVEC4-10); we then examined TNF-α induced lymphocyte adhesion to lymphatic endothelial cells and TNF-α induced expression of MAdCAM-1 and compared these responses to control monolayers. Results Transfection of the IL-10 vector into endothelial cultures significantly reduced TNF-α induced, MAdCAM-1 dependent lymphocyte adhesion (compared to non-transfected cells). IL-10 transfected endothelial cells expressed less than half (46 ± 6.6%) of the MAdCAM-1 induced by TNF-α (set as 100%) in non-transfected (control) cells. Conclusion Our results suggest that gene therapy of the gut microvasculature with IL-10 vectors may be useful in the clinical treatment of IBD. PMID:12625840

  1. Early osteoinductive human bone marrow mesenchymal stromal/stem cells support an enhanced hematopoietic cell expansion with altered chemotaxis- and adhesion-related gene expression profiles

    SciTech Connect

    Sugino, Noriko; Miura, Yasuo; Yao, Hisayuki; Iwasa, Masaki; Fujishiro, Aya; Fujii, Sumie; Hirai, Hideyo; Takaori-Kondo, Akifumi; Maekawa, Taira

    2016-01-22

    Bone marrow (BM) microenvironment has a crucial role in supporting hematopoiesis. Here, by using a microarray analysis, we demonstrate that human BM mesenchymal stromal/stem cells (MSCs) in an early osteoinductive stage (e-MSCs) are characterized by unique hematopoiesis-associated gene expression with an enhanced hematopoiesis-supportive ability. In comparison to BM-MSCs without osteoinductive treatment, gene expression in e-MSCs was significantly altered in terms of their cell adhesion- and chemotaxis-related profiles, as identified with Gene Ontology and Gene Set Enrichment Analysis. Noteworthy, expression of the hematopoiesis-associated molecules CXCL12 and vascular cell adhesion molecule 1 was remarkably decreased in e-MSCs. e-MSCs supported an enhanced expansion of CD34{sup +} hematopoietic stem and progenitor cells, and generation of myeloid lineage cells in vitro. In addition, short-term osteoinductive treatment favored in vivo hematopoietic recovery in lethally irradiated mice that underwent BM transplantation. e-MSCs exhibited the absence of decreased stemness-associated gene expression, increased osteogenesis-associated gene expression, and apparent mineralization, thus maintaining the ability to differentiate into adipogenic cells. Our findings demonstrate the unique biological characteristics of e-MSCs as hematopoiesis-regulatory stromal cells at differentiation stage between MSCs and osteoprogenitor cells and have significant implications in developing new strategy for using pharmacological osteoinductive treatment to support hematopoiesis in hematopoietic stem and progenitor cell transplantation. - Highlights: • Human BM-MSCs in an early osteoinductive stage (e-MSCs) support hematopoiesis. • Adhesion- and chemotaxis-associated gene signatures are altered in e-MSCs. • Expression of CXCL12 and VCAM1 is remarkably decreased in e-MSCs. • e-MSCs are at differentiation stage between MSCs and osteoprogenitor cells. • Osteoinductive treatment

  2. The roles of Tenascin C and Fibronectin 1 in adhesive capsulitis: a pilot gene expression study

    PubMed Central

    Cohen, Carina; Leal, Mariana Ferreira; Belangero, Paulo Santoro; Figueiredo, Eduardo Antônio; Smith, Marília Cardoso; Andreoli, Carlos Vicente; de Castro Pochini, Alberto; Cohen, Moises; Ejnisman, Benno; Faloppa, Flávio

    2016-01-01

    OBJECTIVES: We evaluated mRNA expression levels of genes that encode TGF-β1; the TGF-β1 receptor; the collagen-modifying enzymes LOX, PLOD1, and PLOD2; and the extracellular matrix proteins COMP, FN1, TNC and TNXB in synovial/capsule specimens from patients with idiopathic adhesive capsulitis. Possible associations between the measured mRNA levels and clinical parameters were also investigated. METHODS: We obtained glenohumeral joint synovium/capsule specimens from 9 patients with idiopathic adhesive capsulitis who had not shown improvement in symptoms after 5 months of physiotherapy. Adhesive capsulitis was confirmed in all patients by magnetic resonance imaging. We also obtained specimens from 8 control patients who had underwent surgery for acute acromioclavicular joint dislocation and who had radiological indication of glenohumeral capsule alteration based on arthroscopic evaluation. mRNA expression in the synovium/capsule specimens was analyzed by quantitative reverse transcription PCR. The B2M and HPRT1 genes were used as references to normalize target gene expression in the shoulder tissue samples. RESULTS: The synovium/capsule samples from the patients with adhesive capsulitis had significantly higher TNC and FN1 expression than those from the controls. Additionally, symptom duration directly correlated with expression of TGFβ1 receptor I. CONCLUSION: Elevated levels of TNC and FN1 expression may be a marker of capsule injury. Upregulation of TGFβ1 receptor I seems to be dependent on symptom duration; therefore, TGFβ signaling may be involved in adhesive capsulitis. As such, TNC, FN1 and TGFβ1 receptor I may also play roles in adhesive capsulitis by contributing to capsule inflammation and fibrosis. PMID:27438566

  3. Characterization of the porcine sperm adhesion molecule gene SPAM1- expression analysis, genomic structure, and chromosomal mapping.

    PubMed

    Day, A E; Quilter, C R; Sargent, C A; Mileham, A J

    2002-06-01

    Sequence analysis of cDNA products, derived from adult porcine testis mRNA, gave overlapping nucleotide sequence correlating to 1952 bp of the sperm adhesion molecule 1 (SPAM1) gene. This sequence was shown to be homologous to SPAM1 genes known in other mammalian species and contained an open reading frame encoding a 493-amino acid protein. Fluorescence in situ hybridization (FISH), using a bacterial artificial chromosome (BAC) clone from the PigE BAC library, was used to map SPAM1 to chromosome 18 of the pig. This finding is consistent with comparative mapping experiments performed between pig and human chromosomes. Polymerase chain reaction (PCR) analysis of genomic DNA has shown that the 1952 bp of cDNA sequence spans approximately 9 kb of genomic DNA and comprises of at least four exons, with its size and structure being relatively conserved between mouse, human and pig. Reverse transcriptase (RT)-PCR analysis of mRNA from nine porcine tissues has also suggested that expression of SPAM1 is limited to the testis.

  4. TLR4-mediated expression of Mac-1 in monocytes plays a pivotal role in monocyte adhesion to vascular endothelium.

    PubMed

    Lee, Seung Jin; Choi, Eun Kyoung; Seo, Kyo Won; Bae, Jin Ung; Park, So Youn; Kim, Chi Dae

    2014-01-01

    Toll-like receptor 4 (TLR4) is known to mediate monocyte adhesion to endothelial cells, however, its role on the expression of monocyte adhesion molecules is unclear. In the present study, we investigated the role of TLR4 on the expression of monocyte adhesion molecules, and determined the functional role of TLR4-induced adhesion molecules on monocyte adhesion to endothelial cells. When THP-1 monocytes were stimulated with Kdo2-Lipid A (KLA), a specific TLR4 agonist, Mac-1 expression was markedly increased in association with an increased adhesion of monocytes to endothelial cells. These were attenuated by anti-Mac-1 antibody, suggesting a functional role of TLR4-induced Mac-1 on monocyte adhesion to endothelial cells. In monocytes treated with MK886, a 5-lipoxygenase (LO) inhibitor, both Mac-1 expression and monocyte adhesion to endothelial cells induced by KLA were markedly attenuated. Moreover, KLA increased the expression of mRNA and protein of 5-LO, suggesting a pivotal role of 5-LO on these processes. In in vivo studies, KLA increased monocyte adhesion to aortic endothelium of wild-type (WT) mice, which was attenuated in WT mice treated with anti-Mac-1 antibody as well as in TLR4-deficient mice. Taken together, TLR4-mediated expression of Mac-1 in monocytes plays a pivotal role on monocyte adhesion to vascular endothelium, leading to increased foam cell formation in the development of atherosclerosis.

  5. Biofilm-Forming Staphylococcus epidermidis Expressing Vancomycin Resistance Early after Adhesion to a Metal Surface

    PubMed Central

    Sakimura, Toshiyuki; Kajiyama, Shiro; Adachi, Shinji; Chiba, Ko; Yonekura, Akihiko; Tomita, Masato; Koseki, Hironobu; Miyamoto, Takashi; Tsurumoto, Toshiyuki; Osaki, Makoto

    2015-01-01

    We investigated biofilm formation and time of vancomycin (VCM) resistance expression after adhesion to a metal surface in Staphylococcus epidermidis. Biofilm-forming Staphylococcus epidermidis with a VCM MIC of 1 μg/mL was used. The bacteria were made to adhere to a stainless steel washer and treated with VCM at different times and concentrations. VCM was administered 0, 2, 4, and 8 hours after adhesion. The amount of biofilm formed was evaluated based on the biofilm coverage rates (BCRs) before and after VCM administration, bacterial viability in biofilm was visually observed using the fluorescence staining method, and the viable bacterial count in biofilm was measured. The VCM concentration required to decrease BCR significantly compared with that of VCM-untreated bacteria was 4 μg/mL, even in the 0 hr group. In the 4 and 8 hr groups, VCM could not inhibit biofilm growth even at 1,024 μg/mL. In the 8 hr group, viable bacteria remained in biofilm at a count of 104 CFU even at a high VCM concentration (1,024 μg/mL). It was suggested that biofilm-forming Staphylococcus epidermidis expresses resistance to VCM early after adhesion to a metal surface. Resistance increased over time after adhesion as the biofilm formed, and strong resistance was expressed 4–8 hours after adhesion. PMID:25802873

  6. Cell adhesion and integrin expression are modulated by oxidative stress in EA.hy 926 cells.

    PubMed

    Lamari, Foudil; Braut-Boucher, Francoise; Pongnimitprasert, Nushjira; Bernard, Maguy; Foglietti, Marie-Jose; Derappe, Christian; Aubery, Michele

    2007-07-01

    The effects of oxidative stress on integrin-mediated cell adhesion to the extracellular matrix (ECM) and related apoptosis were investigated using the EA.hy926 endothelial cells treated (or not) with two oxidants: the hypoxanthine/xanthine oxidase system (HX/XO) or the tert-butyl hydroperoxide (t-BHP) which both increased cell apoptosis. Cell adhesion onto vitronectin (Vn) and fibronectin (Fn) was increased at low concentrations of HX/XO (up to 5 mU/ml) or t-BHP (up to 125 microM) and prevented ROS-induced apoptosis. Flow cytometry analysis of integrin expression showed that the expression of integrin alphav and alpha5 subunits was, respectively, increased and decreased. Cell adhesion inhibition experiments using function-blocking monoclonal antibodies against integrin subunits indicated that alphavbeta1 and alphavbeta3 integrins were involved in adhesion of cells to Vn, and alphavbeta3 integrin played a major role in oxidant-treated cells. For adhesion to Fn, alpha5beta1 and alphavbeta1 integrins were required for oxidant-treated cells. Taken together, the results suggest that reactive oxygen species (ROS) produced either by HX/XO or t-BHP could affect expression and/or activation of specific integrins in the interaction of EA.hy926 cells with ECM.

  7. Biofilm-forming Staphylococcus epidermidis expressing vancomycin resistance early after adhesion to a metal surface.

    PubMed

    Sakimura, Toshiyuki; Kajiyama, Shiro; Adachi, Shinji; Chiba, Ko; Yonekura, Akihiko; Tomita, Masato; Koseki, Hironobu; Miyamoto, Takashi; Tsurumoto, Toshiyuki; Osaki, Makoto

    2015-01-01

    We investigated biofilm formation and time of vancomycin (VCM) resistance expression after adhesion to a metal surface in Staphylococcus epidermidis. Biofilm-forming Staphylococcus epidermidis with a VCM MIC of 1 μg/mL was used. The bacteria were made to adhere to a stainless steel washer and treated with VCM at different times and concentrations. VCM was administered 0, 2, 4, and 8 hours after adhesion. The amount of biofilm formed was evaluated based on the biofilm coverage rates (BCRs) before and after VCM administration, bacterial viability in biofilm was visually observed using the fluorescence staining method, and the viable bacterial count in biofilm was measured. The VCM concentration required to decrease BCR significantly compared with that of VCM-untreated bacteria was 4 μg/mL, even in the 0 hr group. In the 4 and 8 hr groups, VCM could not inhibit biofilm growth even at 1,024 μg/mL. In the 8 hr group, viable bacteria remained in biofilm at a count of 10(4) CFU even at a high VCM concentration (1,024 μg/mL). It was suggested that biofilm-forming Staphylococcus epidermidis expresses resistance to VCM early after adhesion to a metal surface. Resistance increased over time after adhesion as the biofilm formed, and strong resistance was expressed 4-8 hours after adhesion.

  8. Spatio-Temporally Restricted Expression of Cell Adhesion Molecules during Chicken Embryonic Development

    PubMed Central

    Roy, Priti; Bandyopadhyay, Amitabha

    2014-01-01

    Differential cell adhesive properties are known to regulate important developmental events like cell sorting and cell migration. Cadherins and protocadherins are known to mediate these cellular properties. Though a large number of such molecules have been predicted, their characterization in terms of interactive properties and cellular roles is far from being comprehensive. To narrow down the tissue context and collect correlative evidence for tissue specific roles of these molecules, we have carried out whole-mount in situ hybridization based RNA expression study for seven cadherins and four protocadherins. In developing chicken embryos (HH stages 18, 22, 26 and 28) cadherins and protocadherins are expressed in tissue restricted manner. This expression study elucidates precise expression domains of cell adhesion molecules in the context of developing embryos. These expression domains provide spatio-temporal context in which the function of these genes can be further explored. PMID:24806091

  9. Kidney Injury Molecule-1: A Translational Journey

    PubMed Central

    Bonventre, Joseph V.

    2014-01-01

    Kidney injury molecule-1 (KIM-1, also named TIM-1 and HAVCR-1) was identified as the most highly upregulated protein in the proximal tubule of the kidney after injury. This protein is present with injury in multiple species including man, and also after a large number of acute and chronic insults to the kidney. It is a type-1 membrane protein whose ectodomain is released into the lumen of the tubule. The ectodomain is heavily glycosylated and stable and appears in the urine after injury. It has been qualified by the United States Food and Drug Administration and the European Medicines Agency for preclinical assessment of nephrotoxicity and on a case-by-case basis for clinical evaluation. As a biomarker in humans, its utility has been demonstrated in acute and chronic injury and in renal cell carcinoma, a condition similar to injury, where there is dedifferentiation of the epithelial cell. KIM-1 is a phosphatidylserine receptor which recognizes apoptotic cells directing them to lysosomes. It also serves as a receptor for oxidized lipoproteins and hence is important for uptake of components of the tubular lumen which may be immunomodulatory and/or toxic to the cell. KIM-1 is unique in being the first molecule, not also present on myeloid cells, that transforms kidney proximal epithelial cells into semi-professional phagocytes. Data suggest that KIM-1 expression is protective during early injury, whereas in chronic disease states, prolonged KIM-1 expression may be maladaptive and may represent a target for therapy of chronic kidney disease. PMID:25125746

  10. Chronic restraint stress down-regulates amygdaloid expression of polysialylated neural cell adhesion molecule.

    PubMed

    Cordero, M I; Rodríguez, J J; Davies, H A; Peddie, C J; Sandi, C; Stewart, M G

    2005-01-01

    The amygdala is a brain area which plays a decisive role in fear and anxiety. Since exposure to chronic stress can induce profound effects in emotion and cognition, plasticity in specific amygdaloid nuclei in response to prior stress has been hypothesized to account for stress-induced emotional alterations. In order to identify amygdala nuclei which may be affected under chronic stress conditions we evaluated the effects of 21-days chronic restraint stress on the expression of a molecule implicated crucially in alterations in structural plasticity: the polysialylated neural cell adhesion molecule. We found that polysialylated neural cell adhesion molecule-immunoreactivity within the amygdala, present in somata and neuronal processes, has a regional gradient with the central medial and medial amygdaloid nuclei showing the highest levels. Our results demonstrate that chronic restraint stress induced an overall reduction in polysialylated neural cell adhesion molecule-immunoreactivity in the amygdaloid complex, mainly due to a significant decrease in the central medial amygdaloid and medial amygdaloid nuclei. Our data suggest that polysialylated neural cell adhesion molecule in these nuclei may play a prominent role in functional and structural remodeling induced by stress, being a potential mechanism for cognitive and emotional modulation. Furthermore, these finding provide the first clear evidence that life experiences can regulate the expression of polysialylated neural cell adhesion molecule in the amygdaloid complex.

  11. Proinflammatory stimuli regulate endothelial hyaluronan expression and CD44/HA-dependent primary adhesion.

    PubMed Central

    Mohamadzadeh, M; DeGrendele, H; Arizpe, H; Estess, P; Siegelman, M

    1998-01-01

    The localization of circulating leukocytes within inflamed tissues occurs as the result of interactions with and migration across vascular endothelium, and is governed, in part, by the expression of adhesion molecules on both cell types. Recently, we have described a novel primary adhesion interaction between the structurally activated form of the adhesion molecule CD44 on lymphocytes and its major ligand hyaluronan on endothelial cells under physiologic laminar flow conditions, and have proposed that this interaction functions in an extravasation pathway for lymphocytes in vascular beds at sites of inflammation. While the regulation of activated CD44 on leukocytes has been characterized in depth, regulation of hyaluronate (HA) on endothelial cells has not been extensively studied. Here we demonstrate that the expression of HA on cultured endothelial cell lines and primary endothelial cultures is inducible by the proinflammatory cytokines TNFalpha and IL-1beta, as well as bacterial lipopolysaccharide. In addition, this inducibility appears strikingly restricted to endothelial cells derived from microvascular, but not large vessel, sources. The elevated HA levels thus induced result in increased CD44-dependent adhesive interactions in both nonstatic shear and laminar flow adhesion assays. Changes in mRNA levels for the described HA synthetic and degradative enzymes were not found, suggesting other more complex mechanisms of regulation. Together, these data add to the selectin and immunoglobulin gene families a new inducible endothelial adhesive molecule, hyaluronan, and help to further our understanding of the potential physiologic roles of the CD44/HA interaction; i.e., local cytokine production within inflamed vascular beds may enhance surface hyaluronan expression on endothelial cells, thereby creating local sites receptive to the CD44/HA interaction and thus extravasation of inflammatory cells. PMID:9421471

  12. Differential expression of cell adhesion molecules in an ionizing radiation-induced breast cancer model system.

    PubMed

    Calaf, Gloria M; Roy, Debasish; Narayan, Gopeshwar; Balajee, Adayabalam S

    2013-07-01

    Cell-cell adhesion is mediated by members of the cadherin-catenin system and among them E-cadherin and β-catenin are important adhesion molecules for epithelial cell function and preservation of tissue integrity. To investigate the importance of cell adhesion molecules in breast carcinogenesis, we developed an in vitro breast cancer model system wherein immortalized human breast epithelial cell line, MCF-10F, was malignantly transformed by exposure to low doses of high linear energy transfer (LET) α particle radiation (150 keV/µm) and subsequent growth in the presence or absence of 17β-estradiol. This model consisted of human breast epithelial cells in different stages of transformation: i) parental cell line MCF-10F; ii) MCF-l0F continuously grown with estradiol at 10(-8) (Estrogen); iii) a non-malignant cell line (Alpha3); and iv) a malignant and tumorigenic cell line (Alpha5) and the Tumor2 cell line derived from the nude mouse xenograft of the Alpha5 cell line. Expression levels of important cell adhesion molecules such as α-catenin, β-catenin, γ-catenin, E-cadherin and integrin were found to be higher at the protein level in the Alpha5 and Tumor2 cell lines relative to these levels in the non-tumorigenic MCF-10F, Estrogen and Alpha3 cell lines. In corroboration, cDNA expression analysis revealed elevated levels of genes involved in the cell adhesion function [E-cadherin, integrin β6 and desmocollin3 (DSc3)] in the Alpha5 and Tumor2 cell lines relative to the levels in the MCF-10F, Estrogen and Alpha3 cell lines. Collectively, our results suggest that cell adhesion molecules are expressed at higher levels in malignantly transformed breast epithelial cells relative to levels in non-malignant cells. However, reduced levels of adhesion molecules observed in the mouse xenograft-derived Tumor 2 cell line compared to the pre-tumorigenic Alpha5 cell line suggests that the altered expression levels of adhesion molecules depend on the tumor tissue

  13. Expression of leukocyte-endothelial cell adhesion molecules on monocyte adhesion to human endothelial cells on plasma treated PET and PTFE in vitro.

    PubMed

    Pu, F R; Williams, R L; Markkula, T K; Hunt, J A

    2002-12-01

    We used a coculture model to evaluate the inflammatory potential of ammonia gas plasma modified PET and PTFE by flow cytometry and immunohistochemistry. In these studies, human endothelial cells from umbilical cord (HUVEC) and promonocytic U937 cells were used. HUVECs grown on polystyrene tissue culture coverslips and HUVECs stimulated with tumour necrosis factor (TNF-alpha) were used as controls. U937 adhesion to endothelium on each surface was evaluated at day 1 and day 7. To further investigate the role of leukocyte-endothelial cell adhesion molecules (CAMs) in cell-to-cell interaction on material surfaces, the expression of the leukocyte-endothelial CAMs: ICAM-1, VCAM-1, PECAM-1, and E-selectin on HUVECs were evaluated after U937 cell adhesion. The results demonstrated that plasma treated PET (T-PET) and treated PTFE (T-PTFE) did not increase U937 cell adhesion compared to the negative control. Maximal adhesion of U937 cells to HUVEC was observed on TNF-alpha stimulated endothelium with significant differences between day 1 and day 7, which is consistent with our prior observation that T-PET and T-PTFE did not cause HUVECs to increase the expression of adhesion molecules. After U937 cell adhesion, the expression of ICAM-1 and VCAM-1 of HUVECs were not different on T-PET and T-PTFE compared with the negative control. However, the expression of E-selectin was reduced on day 1, but not on day 7. The effects of plasma treated PET and PTFE on HUVEC adhesion and proliferation were also studied. On day 1 there were slight increases in the growth of HUVECs on both of T-PET and T-PTFE but this was not statistically significant. On day 7, the cell number increased significantly on the surfaces compared to the negative control. The results demonstrate that the plasma treatment of PET and PTFE with ammonia improves the adhesion and growth of endothelial cells and these surfaces do not exhibit a direct inflammatory effect in terms of monocyte adhesion and expression of

  14. [The effect of adhesion molecule CEACAM1 and chemokine receptor CXCR4 expression on prognosis of non-small cell lung cancer patients].

    PubMed

    Yurdakul, Ahmet Selim; Akyürek, Nalan; Demirtaş, Senay; Karakaya, Jale; Memiş, Leyla; Oztürk, Can

    2010-01-01

    Poor prognosis in the lung cancer result from early metastatic potential of the tumoral cells. The mechanisms of tumoral cell metastasis are complex. Adhesion molecules play an important role in metastatic process, which is cell-to-cell and cell-to-matrix interactions and chemokins which arrange the migration and growth of the cells are also important in metastatic biology. The aim of this study is to investigate the prognostic relevance of carcinoembrionic antigen cell adhesion molecule 1 (CEACAM1) and chemokine receptor CXCR4 expression in patients with non-small cell lung cancer (NSCLC). Using immunohistochemical analysis, we evaluated CEACAM1 and CXCR4 expression in parafine specimens from 50 patients with NSCLC confirmed histopathologically and the relationship between CEACAM1 and CXCR4 expression and the prognosis. Twenty-one (42%) patients were positive and 29 (58%) were negative for CEACAM1 expression. Patients whose tumors had CEACAM1-positive staining had a shorter duration of survival than patients whose tumors had no expression, but it was not significant statistically [8.93 ± 8, (median: 8) vs 12.3 ± 11.3, (median: 9), p> 0.36]. Twenty-three (46%) patients were positive and 27 (54%) were negative for CXCR4 expression. Patients whose tumors had CXCR4-positive staining had a longer duration of survival than patients whose tumors had no expression, but it was not significant statistically [12.8 ± 12.4, (median: 12) vs 9.3 ± 7.6, (median: 8), p> 0.14]. In conclusion, CEACAM1 and CXCR4 played a part in metastatic process in lung cancer may not affect on survival independently. The biologic mechanisms leading to the spread of tumor cells are complex and related multifactoriel process.

  15. Biophysically inspired model for functionalized nanocarrier adhesion to cell surface: roles of protein expression and mechanical factors

    PubMed Central

    Ramakrishnan, N.; Tourdot, Richard W.; Eckmann, David M.; Ayyaswamy, Portonovo S.; Muzykantov, Vladimir R.; Radhakrishnan, Ravi

    2016-01-01

    In order to achieve selective targeting of affinity–ligand coated nanoparticles to the target tissue, it is essential to understand the key mechanisms that govern their capture by the target cell. Next-generation pharmacokinetic (PK) models that systematically account for proteomic and mechanical factors can accelerate the design, validation and translation of targeted nanocarriers (NCs) in the clinic. Towards this objective, we have developed a computational model to delineate the roles played by target protein expression and mechanical factors of the target cell membrane in determining the avidity of functionalized NCs to live cells. Model results show quantitative agreement with in vivo experiments when specific and non-specific contributions to NC binding are taken into account. The specific contributions are accounted for through extensive simulations of multivalent receptor–ligand interactions, membrane mechanics and entropic factors such as membrane undulations and receptor translation. The computed NC avidity is strongly dependent on ligand density, receptor expression, bending mechanics of the target cell membrane, as well as entropic factors associated with the membrane and the receptor motion. Our computational model can predict the in vivo targeting levels of the intracellular adhesion molecule-1 (ICAM1)-coated NCs targeted to the lung, heart, kidney, liver and spleen of mouse, when the contributions due to endothelial capture are accounted for. The effect of other cells (such as monocytes, etc.) do not improve the model predictions at steady state. We demonstrate the predictive utility of our model by predicting partitioning coefficients of functionalized NCs in mice and human tissues and report the statistical accuracy of our model predictions under different scenarios. PMID:27429783

  16. Biophysically inspired model for functionalized nanocarrier adhesion to cell surface: roles of protein expression and mechanical factors.

    PubMed

    Ramakrishnan, N; Tourdot, Richard W; Eckmann, David M; Ayyaswamy, Portonovo S; Muzykantov, Vladimir R; Radhakrishnan, Ravi

    2016-06-01

    In order to achieve selective targeting of affinity-ligand coated nanoparticles to the target tissue, it is essential to understand the key mechanisms that govern their capture by the target cell. Next-generation pharmacokinetic (PK) models that systematically account for proteomic and mechanical factors can accelerate the design, validation and translation of targeted nanocarriers (NCs) in the clinic. Towards this objective, we have developed a computational model to delineate the roles played by target protein expression and mechanical factors of the target cell membrane in determining the avidity of functionalized NCs to live cells. Model results show quantitative agreement with in vivo experiments when specific and non-specific contributions to NC binding are taken into account. The specific contributions are accounted for through extensive simulations of multivalent receptor-ligand interactions, membrane mechanics and entropic factors such as membrane undulations and receptor translation. The computed NC avidity is strongly dependent on ligand density, receptor expression, bending mechanics of the target cell membrane, as well as entropic factors associated with the membrane and the receptor motion. Our computational model can predict the in vivo targeting levels of the intracellular adhesion molecule-1 (ICAM1)-coated NCs targeted to the lung, heart, kidney, liver and spleen of mouse, when the contributions due to endothelial capture are accounted for. The effect of other cells (such as monocytes, etc.) do not improve the model predictions at steady state. We demonstrate the predictive utility of our model by predicting partitioning coefficients of functionalized NCs in mice and human tissues and report the statistical accuracy of our model predictions under different scenarios.

  17. Biophysically inspired model for functionalized nanocarrier adhesion to cell surface: roles of protein expression and mechanical factors

    NASA Astrophysics Data System (ADS)

    Ramakrishnan, N.; Tourdot, Richard W.; Eckmann, David M.; Ayyaswamy, Portonovo S.; Muzykantov, Vladimir R.; Radhakrishnan, Ravi

    2016-06-01

    In order to achieve selective targeting of affinity-ligand coated nanoparticles to the target tissue, it is essential to understand the key mechanisms that govern their capture by the target cell. Next-generation pharmacokinetic (PK) models that systematically account for proteomic and mechanical factors can accelerate the design, validation and translation of targeted nanocarriers (NCs) in the clinic. Towards this objective, we have developed a computational model to delineate the roles played by target protein expression and mechanical factors of the target cell membrane in determining the avidity of functionalized NCs to live cells. Model results show quantitative agreement with in vivo experiments when specific and non-specific contributions to NC binding are taken into account. The specific contributions are accounted for through extensive simulations of multivalent receptor-ligand interactions, membrane mechanics and entropic factors such as membrane undulations and receptor translation. The computed NC avidity is strongly dependent on ligand density, receptor expression, bending mechanics of the target cell membrane, as well as entropic factors associated with the membrane and the receptor motion. Our computational model can predict the in vivo targeting levels of the intracellular adhesion molecule-1 (ICAM1)-coated NCs targeted to the lung, heart, kidney, liver and spleen of mouse, when the contributions due to endothelial capture are accounted for. The effect of other cells (such as monocytes, etc.) do not improve the model predictions at steady state. We demonstrate the predictive utility of our model by predicting partitioning coefficients of functionalized NCs in mice and human tissues and report the statistical accuracy of our model predictions under different scenarios.

  18. The Effect of Glass Ionomer and Adhesive Cements on Substance P Expression in Human Dental Pulp

    PubMed Central

    Ariza-Garcia, German; Camelo, Patricia; Mejia, Monica; Ojeda, Karyn; Azuero-Holguin, Maria M.; Abad-Coronel, Dunia; Munoz, Hugo R.

    2013-01-01

    Objectives: The purpose of this study was to quantify the effect of glass ionomer and adhesive cements on SP expression in healthy human dental pulp. Study Design: Forty pulp samples were obtained from healthy premolars where extraction was indicated for orthodontic reasons. In thirty of these premolars a Class V cavity preparation was performed and teeth were equally divided in three groups: Experimental Group I: Glass Ionomer cement was placed in the cavity. Experimental Group II: Adhesive Cement was placed in the cavity. Positive control group: Class V cavities only. The remaining ten healthy premolars where extracted without treatment and served as a negative control group. All pulp samples were processed and SP was measured by radioimmunoassay. Results: Greater SP expression was found in the adhesive cement group, followed by the glass ionomer and the positive control groups. The lower SP values were for the negative control group. ANOVA showed statistically significant differences between groups (p<0.0001). Tukey HSD post hoc tests showed statistically significant differences in SP expression between negative control group and the 3 other groups (p<0.01). Differences between the cavity-only group and the two experimental groups were also statistically significant (p<0.05 and p<0.01 respectively). There is also a statistically significant difference between the two experimental groups (p<0.01). Conclusions: These findings suggest that adhesive cements provoke a greater SP expression when compared with glass ionomer. Key words:Glass Ionomer, adhesive cement, Substance P, human dental pulp. PMID:23722145

  19. Adhesion molecules expression in CLL: Potential impact on clinical and hematological parameters.

    PubMed

    Kamel, Azza M; El-Sharkawy, Nahla M; Osman, Randa A; Abd El-Fattah, Eman K; El-Noshokaty, Essam; Abd El-Hamid, Thoraya; Kandeel, Eman Z

    2016-03-01

    B-cell chronic lymphocytic leukemia (CLL) is marked by the accumulation of CD5+ B lymphocytes within the blood, bone marrow (BM), and secondary lymphoid tissues. Abnormalities in the expression and function of cell adhesion molecules may account for the patterns of intra-nodal growth and hematogenous spread of the malignant cells. Chemokines and integrin-mediated adhesion and trans-endothelial migration (TEM) are central aspects in trafficking and retention of hematopoietic cells in the BM and lymphoid organs. This work was conducted to study adhesion molecules status in CLL and its potential impact on both hematological and clinical parameters. The study included 78 newly diagnosed CLL patients. Immunophenotyping was performed on peripheral blood using the chronic lymphoid panel. Adhesion molecules (CD11a, CD11b, CD49d, CD49C, CD29 and CD38) were tested using monoclonal antibodies and analyzed by Flow Cytometry. Positive correlation was encountered between adhesion molecules: CD38 with CD49d (r=0.25, p=0.028), CD11a with CD11b, CD49d and CD29 (r=0.394, p=0.001; r=0.441, p=<0.01 and r=0.446, p<0.01 respectively) and CD29 with CD49c and CD49d (r=0.437, p<0.01; r=0.674, p<0.01 respectively). CD49c showed negative correlation with Rai staging (r=-0.269, p=0.033). CD11a and CD29 showed a significant relation with splenomegaly (p=0.04 and 0.03 respectively) and CD49d showed a significant relation with lymphadenopathy (p=0.02). The level of different adhesion molecules expression in CLL is apparently reflected on the potential migratory behavior of the leukemic cells to different organs. Copyright © 2016 National Cancer Institute, Cairo University. Production and hosting by Elsevier B.V. All rights reserved.

  20. Galectin-7 acts as an adhesion molecule during implantation and increased expression is associated with miscarriage.

    PubMed

    Menkhorst, E M; Gamage, T; Cuman, C; Kaitu'u-Lino, T J; Tong, S; Dimitriadis, E

    2014-03-01

    Galectins are expressed at the fetal-maternal interface and have multiple roles including during blastocyst implantation. The expression of galectin-7 however has not been investigated in the uterus. We aimed to localise galectin-7 to the endometrium of women with normal fertility and with a history of miscarriage and prospectively determine whether serum levels are altered in women who subsequently miscarry. We also investigated the role of galectin-7 on trophoblast-endometrial epithelial cell adhesion. Immunohistochemistry localised galectin-7 to endometrium throughout the menstrual cycle in women (normal fertility or with history of miscarriage) and in first trimester implantation sites. Galectin-7 serum levels were determined by ELISA. We used both endometrial epithelial-trophoblast cell lines and primary cells for cell-cell adhesion experiments. Galectin-7 immunolocalized to endometrial luminal and glandular epithelium in normally fertile women and was upregulated in epithelium and stroma of women with a history of miscarriage. Similarly, galectin-7 serum levels were elevated at 6 weeks gestation in women who subsequently miscarried compared to gestation matched controls. Exogenous galectin-7 reduced endometrial epithelial-trophoblast adhesion in cell-line and primary cell assays. However, when endometrial epithelial cells were isolated from women with endometrial disorders, galectin-7 increased epithelial-trophoblast adhesion. Galectin-7 is produced by endometrial epithelium and is abnormally elevated in the endometrium of women with a history of miscarriage. Serum levels may be useful as a predictive biomarker of miscarriage. Our data suggests that galectin-7 facilitates adhesion of the embryo to the endometrium and elevated galectin-7 may result in abnormal adhesion. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Endothelial Cell Junctional Adhesion Molecules: Role and Regulation of Expression in Inflammation.

    PubMed

    Reglero-Real, Natalia; Colom, Bartomeu; Bodkin, Jennifer Victoria; Nourshargh, Sussan

    2016-10-01

    Endothelial cells line the lumen of all blood vessels and play a critical role in maintaining the barrier function of the vasculature. Sealing of the vessel wall between adjacent endothelial cells is facilitated by interactions involving junctionally expressed transmembrane proteins, including tight junctional molecules, such as members of the junctional adhesion molecule family, components of adherence junctions, such as VE-Cadherin, and other molecules, such as platelet endothelial cell adhesion molecule. Of importance, a growing body of evidence indicates that the expression of these molecules is regulated in a spatiotemporal manner during inflammation: responses that have significant implications for the barrier function of blood vessels against blood-borne macromolecules and transmigrating leukocytes. This review summarizes key aspects of our current understanding of the dynamics and mechanisms that regulate the expression of endothelial cells junctional molecules during inflammation and discusses the associated functional implications of such events in acute and chronic scenarios. © 2016 American Heart Association, Inc.

  2. Lipopolysaccharide induces VCAM-1 expression and neutrophil adhesion to human tracheal smooth muscle cells: Involvement of Src/EGFR/PI3-K/Akt pathway

    SciTech Connect

    Lin, W.-N.; Luo, S.-F.; Wu, C.-B.; Lin, C.-C.; Yang, C.-M.

    2008-04-15

    In our previous study, LPS has been shown to induce vascular cell adhesion molecule-1(VCAM-1) expression through MAPKs and NF-{kappa}B in human tracheal smooth muscle cells (HTSMCs). In addition to these pathways, the non-receptor tyrosine kinases (Src), EGF receptor (EGFR), and phosphatidylinositol 3-kinase (PI3K) have been shown to be implicated in the expression of several inflammatory target proteins. Here, we reported that LPS-induced up-regulation of VCAM-1 enhanced the adhesion of neutrophils onto HTSMC monolayer, which was inhibited by LY294002 and wortmannin. LPS stimulated phosphorylation of protein tyrosine kinases including Src, PYK2, and EGFR, which were further confirmed using specific anti-phospho-Src, PYK2, or EGFR Ab, respectively, revealed by Western blotting. LPS-stimulated Src, PYK2, EGFR, and Akt phosphorylation and VCAM-1 expression were attenuated by the inhibitors of Src (PP1), EGFR (AG1478), PI3-K (LY294002 and wortmannin), and Akt (SH-5), respectively, or transfection with siRNAs of Src or Akt and shRNA of p110. LPS-induced VCAM-1 expression was also blocked by pretreatment with curcumin (a p300 inhibitor) or transfection with p300 siRNA. LPS-stimulated Akt activation translocated into nucleus and associated with p300 and VCAM-1 promoter region was further confirmed by immunofluorescence, immunoprecipitation, and chromatin immunoprecipitation assays. This association of Akt and p300 to VCAM-1 promoter was inhibited by pretreatment with PP1, AG1478, wortmannin, and SH-5. LPS-induced p300 activation enhanced VCAM-1 promoter activity and VCAM-1 mRNA expression. These results suggested that in HTSMCs, Akt phosphorylation mediated through transactivation of Src/PYK2/EGFR promoted the transcriptional p300 activity and eventually led to VCAM-1 expression induced by LPS.

  3. Correlating the kinetics of cytokine-induced E-selectin adhesion and expression on endothelial cells.

    PubMed Central

    Levin, J D; Ting-Beall, H P; Hochmuth, R M

    2001-01-01

    Many human diseases are mediated through the immune system. In chronic inflammatory disorders, the processes ordinarily involved in tissue healing become destructive. Endothelial cells normally recruit leukocytes to inflamed tissue using cytokine-induced adhesion receptors on the surfaces of interacting cells. Leukocyte capture depends on specialized characteristics of these receptors, particularly the binding kinetics. This study is designed to clarify the relationship between cytokine-induced changes in cell properties and binding kinetics. Here, we measure the kinetics of expression and monoclonal antibody binding for E-selectin in interleukin-1alpha-stimulated microvascular endothelium in vitro and incorporate the data into kinetic models. Quantitative flow cytometry is used to determine molecular density (expression), and micropipette assays are used to find the probability of adhesion (function). Within five hours of interleukin-1alpha stimulation, E-selectin density increases from 0 to 742 sites/microm(2), and antibody-E-selectin adhesion probability increases from a baseline of 6.3% to 64%. A kinetic model is applied to find an apparent association rate constant, k(f), of 3.7 x 10(-14) cm(2)/sec for antibody-E-selectin binding. Although the model successfully predicts experimental results, the rate constant is undervalued for a diffusion-limited process, suggesting that functional adhesion may be modified through cytokine-induced changes in microtopology and receptor localization. PMID:11159434

  4. Exenatide Alters Gene Expression of Neural Cell Adhesion Molecule (NCAM), Intercellular Cell Adhesion Molecule (ICAM), and Vascular Cell Adhesion Molecule (VCAM) in the Hippocampus of Type 2 Diabetic Model Mice

    PubMed Central

    Gumuslu, Esen; Cine, Naci; Gökbayrak, Merve Ertan; Mutlu, Oguz; Celikyurt, Ipek Komsuoglu; Ulak, Guner

    2016-01-01

    Background Glucagon-like peptide-1 (GLP-1), a potent and selective agonist for the GLP-1 receptor, ameliorates the symptoms of diabetes through stimulation of insulin secretion. Exenatide is a potent and selective agonist for the GLP-1 receptor. Cell adhesion molecules are members of the immunoglobulin superfamily and are involved in synaptic rearrangements in the mature brain. Material/Methods The present study demonstrated the effects of exenatide treatment (0.1 μg/kg, subcutaneously, twice daily for 2 weeks) on the gene expression levels of cell adhesion molecules, neural cell adhesion molecule (NCAM), intercellular cell adhesion molecule (ICAM), and vascular cell adhesion molecule (VCAM) in the brain tissue of diabetic BALB/c male mice by real-time quantitative polymerase chain reaction (PCR). Diabetes was induced by streptozotocin/nicotinamide (STZ-NA) injection to male mice. Results The results of this study revealed that hippocampal gene expression of NCAM, ICAM, and VCAM were found to be up-regulated in STZ-NA-induced diabetic mice compared to those of controls. A significant decrease in the gene expression levels of NCAM, ICAM, and VCAM were determined after 2 weeks of exenatide administration. Conclusions Cell adhesion molecules may be involved in the molecular mechanism of diabetes. Exenatide has a strong beneficial action in managing diabetes induced by STZ/NA by altering gene expression of NCAM, ICAM, and VCAM. PMID:27465247

  5. [Expression of apoptosis markers in adhesions in the abdominal cavity under the experimental conditions].

    PubMed

    Shurygina, N A; Shurygin, M G; Aiushinova, N I

    2014-01-01

    Our aim was to study the expression of markers of caspase-dependent and caspase-independent apoptosis pathway activation in the process of repair in case of damage of the serous membrane of the abdominal cavity. On the experimental model of adhesions in the abdominal cavity (male rats Wistar, n = 40) in dynamics from 2 hours to 30 days after injury to the peritoneum studied marker expression pro-apoptosis (Bcl-x) and anti-apoptosis (Bcl-2), and PARP-1. It was found that in the conditions of traumatic injury of the peritoneum apoptosis and anti-apoptosis occur in parallel. In the initial period of the anti-apoptosis mechanisms prevail, and in later periods dominated phenomena pro-apoptosis. PARP-1 activation indicates an increase in the frequency of DNA damage cells, and the duration of this process stimulates cell death by caspase-independent pathway. Together, these processes result in the elimination of a large number of cells, especially fibroblast of zone connective tissue formation in an aseptic area of inflammation in the peritoneal injury. We first established that in the case of peritoneal injury marker expression of anti-apoptosis in the damage zone has the character of the two-wave with maximum expression at 1-third day of the pathological process with repetitive peak on the 14th day. Identifying key parts of apoptosis in the formation of adhesions in the abdominal cavity, which can be used for the development of drugs for the prevention of adhesions.

  6. Murine MicroRNA-214 regulates intracellular adhesion molecule (ICAM1) gene expression in genital Chlamydia muridarum infection

    PubMed Central

    Arkatkar, Tanvi; Gupta, Rishein; Li, Weidang; Yu, Jieh-Juen; Wali, Shradha; Neal Guentzel, M; Chambers, James P; Christenson, Lane K; Arulanandam, Bernard P

    2015-01-01

    The hallmark of chlamydial infection is the development of upper genital pathology in the form of hydrosalpinx and oviduct and/or tubal dilatation. Although molecular events leading to genital tissue presentation and cellular architectural remodelling are unclear, early-stage host immune responses are believed to contribute to these long-term sequelae. Recently, we reported the contribution of selected infection-associated microRNAs (miRs) in the generation of host immunity at early-stage infection (day 6 after intravaginal Chlamydia muridarum challenge in C57BL/6 mice). In this report, we describe the contribution of an infection-associated microRNA, i.e. miR-214, to host immunity. Chlamydia muridarum infection in the C57BL/6 mouse genital tract significantly down-regulated miR-214 while up-regulating intracellular adhesion molecule 1 (ICAM1) gene expression. These in vivo observations were confirmed by establishing direct regulation of ICAM-1 by miR-214 in ex vivo genital cell cultures in the presence of miR-214 mimic and inhibitor. Because, ICAM-1 contributes to recruitment of neutrophils following infection, we also demonstrated that alteration of ICAM1 by miR-214 in interleukin-17A-deficient (IL-17A−/−) mice correlated with reduction of neutrophils infiltrating genital tissue at day 6 after challenge. Additionally, these early-stage events resulted in significantly decreased genital pathology in IL-17A−/− mice compared with C57BL/6 mice. This report provides evidence for early-stage regulation of ICAM1 by microRNAs, resulting in reduction of genital pathology associated with chlamydial infection. PMID:25865776

  7. Cytokine and adhesion molecule expression in primary human endothelial cells stimulated with fever-range hyperthermia.

    PubMed

    Shah, A; Unger, E; Bain, M D; Bruce, R; Bodkin, J; Ginnetti, J; Wang, W C; Seon, B; Stewart, C C; Evans, S S

    2002-01-01

    Migration of blood-borne lymphocytes into lymphoid tissues and sites of inflammation is initiated by vascular adhesion molecules and proinflammatory cytokines. Previous in vivo studies have shown that febrile temperatures dynamically stimulate adhesion in differentiated high endothelial venules (HEV), which are portals for lymphocyte extravasation. This report examines the direct effect of fever-range hyperthermia on the expression of adhesion molecules and cytokines by primary cultured endothelial cells. In both macrovascular (HUVEC) and microvascular (HMVEC) endothelial cells, fever-range hyperthermia (40 degrees C for 6-12 h) did not affect expression of adhesion molecules (ICAM-1, E-selectin, VCAM-1, P-selectin, PECAM-1, PNAd, MAdCAM-1), cytokine release (IL-1beta, TNF-alpha, IFN-gamma, IL-6, IL-11, IL-12, IL-13), or chemokine secretion (IL-8, RANTES, MCP-1, MIP-1beta, MIG). This is in contrast to the stimulatory effects of TNF-alpha or 43 degrees C heat shock. However, a novel role for fever-range hyperthermia was identified in augmenting actin polymerization in cultured endothelial cells and enhancing the ability of endothelial-derived factors to transactivate the alpha4beta7 integrin lymphocyte homing receptor. These findings provide insight into the tightly regulated effects of fever-range hyperthermia that exclude induction of adhesion in non-activated endothelium of normal blood vessels. Through these mechanisms, it is proposed that febrile temperatures associated with infection or clinical hyperthermia avoid the unproductive exodus of lymphocytes to non-involved extralymphoid tissues while simultaneously promoting lymphocyte delivery to sites of immune activation.

  8. Recombinant Probiotic Expressing Listeria Adhesion Protein Attenuates Listeria monocytogenes Virulence In Vitro

    PubMed Central

    Koo, Ok Kyung; Amalaradjou, Mary Anne Roshni; Bhunia, Arun K.

    2012-01-01

    Background Listeria monocytogenes, an intracellular foodborne pathogen, infects immunocompromised hosts. The primary route of transmission is through contaminated food. In the gastrointestinal tract, it traverses the epithelial barrier through intracellular or paracellular routes. Strategies to prevent L. monocytogenes entry can potentially minimize infection in high-risk populations. Listeria adhesion protein (LAP) aids L. monocytogenes in crossing epithelial barriers via the paracellular route. The use of recombinant probiotic bacteria expressing LAP would aid targeted clearance of Listeria from the gut and protect high-risk populations from infection. Methodology/Principal Findings The objective was to investigate the ability of probiotic bacteria or LAP-expressing recombinant probiotic Lactobacillus paracasei (LbpLAP) to prevent L. monocytogenes adhesion, invasion, and transwell-based transepithelial translocation in a Caco-2 cell culture model. Several wild type probiotic bacteria showed strong adhesion to Caco-2 cells but none effectively prevented L. monocytogenes infection. Pre-exposure to LbpLAP for 1, 4, 15, or 24 h significantly (P<0.05) reduced adhesion, invasion, and transepithelial translocation of L. monocytogenes in Caco-2 cells, whereas pre-exposure to parental Lb. paracasei had no significant effect. Similarly, LbpLAP pre-exposure reduced L. monocytogenes translocation by as much as 46% after 24 h. LbpLAP also prevented L. monocytogenes-mediated cell damage and compromise of tight junction integrity. Furthermore, LbpLAP cells reduced L. monocytogenes-mediated cell cytotoxicity by 99.8% after 1 h and 79% after 24 h. Conclusions/Significance Wild type probiotic bacteria were unable to prevent L. monocytogenes infection in vitro. In contrast, LbpLAP blocked adhesion, invasion, and translocation of L. monocytogenes by interacting with host cell receptor Hsp60, thereby protecting cells from infection. These data show promise for the use of recombinant

  9. Sulfone derivatives reduce growth, adhesion and aspartic protease SAP2 gene expression.

    PubMed

    Bondaryk, Małgorzata; Ochal, Zbigniew; Staniszewska, Monika

    2014-09-01

    Fungal virulence factors represent a strategy for the design of new compounds with effective activities against Candida spp. Dichloromethyl-4-chloro-3-nitrophenylsulfone (named Compound 1) and chlorodibromomethyl-4-hydrazino-3-nitrophenylsulfone (Compound 2) versus Candida albicans virulence factors (SAP2 expression and adhesion to Caco-2 cell line) were investigated. Candida albicans SC5314 and its mutants: Δsap9, Δsap10, Δsap9/10 were used. MICs of the Compounds (concentrated at 0.0313-16 µg/ml) were determined using M27-A3. Percentage of cell inhibition was assessed spectrophotometrically (OD405) after 48 h at 35 °C. The SAP2 expression was analyzed with the use of RT-PCR; relative quantification was normalized against ACT1 in cells grown in YEPD and on Caco-2. Adherence assay of C. albicans to Caco-2 was performed in a 24-well-plate. Compound 1 showed higher activity (% = 100 at 4 µg/ml) than Compound 2 (MIC90 = 16 µg/ml). Dichloromethyl at the para position of the phenyl ring exerted anti-Candidal potential. Under Compound 1, SAP2 was down-regulated in all the strains (P ≤ 0.05). Conversely, SAP2 was over-expressed in Δsap9-10 (untreated cells) compared with the wild-type. The Compounds significantly affected adherence to epithelium (P ≤ 0.05). The tested sulfones interfered with the adhesion of C. albicans cells to the epithelial tissues without affecting their viability after 90-min of incubation. The Compounds' mode of action was attributed to the reduced adhesiveness and the lower SAP2 expression. Saps9-10 play a role in C. albicans adhesion and they can be involved in the sulfone resistance mechanisms.

  10. Decrease of breast cancer cell invasiveness by sodium phenylacetate (NaPa) is associated with an increased expression of adhesive molecules.

    PubMed

    Vasse, M; Thibout, D; Paysant, J; Legrand, E; Soria, C; Crépin, M

    2001-03-23

    Sodium phenylacetate (NaPa), a non-toxic phenylalanine metabolite, has been shown to induce in vivo and in vitro cytostatic and antiproliferative effects on various cell types. In this work, we analysed the effect of NaPa on the invasiveness of breast cancer cell (MDA-MB-231, MCF-7 and MCF-7 ras). Using the highly invasive breast cancer cell line MDA-MB-231, we demonstrated that an 18-hour incubation with NaPa strongly inhibits the cell invasiveness through Matrigel (86% inhibition at 20 mM of NaPa). As cell invasiveness is greatly influenced by the expression of urokinase (u-PA) and its cell surface receptor (u-PAR) as well as the secretion of matrix metalloproteinases (MMP), we tested the effect of NaPa on these parameters. An 18-hour incubation with NaPa did not modify u-PA expression, either on MDA-MB-231 or on MCF-7 and MCF-7 ras cell lines, and induced a small u-PA decrease after 3 days of treatment of MDA-MB-321 with NaPa. In contrast, an 18 h incubation of MDA-MB-231 increased the expression of u-PAR and the secretion of MMP-9. As u-PAR is a ligand for vitronectin, a composant of the extracellular matrix, these data could explain the increased adhesion of MDA-MB-231 to vitronectin, while cell adhesivity of MCF-7 and MCF-7 ras was unmodified by NaPa treatment. NaPa induced also an increased expression of both Lymphocyte Function-Associated-1 (LFA-1) and Intercellular Adhesion Molecule-1 (ICAM-1), which was obvious from 18 hour incubation with NaPa for the MDA-MB-231 cells, but was delayed (3 days) for MCF-7 and MCF-7 ras. Only neutralizing antibodies against LFA-1 reversed the decreased invasiveness of NaPa-treated cells. Therefore we can conclude that the strong inhibition of MDA-MB-231 invasiveness is not due to a decrease in proteases involved in cell migration (u-PA and MMP) but could be related both to the modification of cell structure and an increased expression of adhesion molecules such as u-PAR and LFA-1.

  11. Altered expression of adhesion molecules on peripheral blood leukocytes in feline infectious peritonitis.

    PubMed

    Olyslaegers, Dominique A J; Dedeurwaerder, Annelike; Desmarets, Lowiese M B; Vermeulen, Ben L; Dewerchin, Hannah L; Nauwynck, Hans J

    2013-10-25

    Feline infectious peritonitis (FIP) is a fatal, coronavirus-induced systemic disease in domestic and wild felids. The pathology associated with FIP (multifocal granulomatous vasculitis) is considered to be elicited by exaggerated activation and subsequent extravasation of leukocytes. As changes in the expression of adhesion molecules on circulating leukocytes precede their margination and emigration, we reasoned that the expression of leukocyte adhesion molecules may be altered in FIP. In present study, the expression of principal adhesion molecules involved in leukocyte transmigration (CD15s, CD11a, CD11b, CD18, CD49d, and CD54) on peripheral blood leukocytes from cats with naturally occurring FIP (n=15) and controls (n=12) was quantified by flow cytometry using a formaldehyde-based rapid leukocyte preparation technique. T- and B-lymphocytes from FIP patients exhibit higher expression of both subunits (CD11a and CD18) composing the β2 integrin lymphocyte function-associated antigen (LFA)-1. In addition, the expression of the α4 subunit (CD49d) of the β1 integrin very late antigen (VLA)-4 was elevated on B-lymphocytes from FIP patients. The expression of CD11b and CD18, that combine to form the β2 integrin macrophage-1 antigen (Mac-1), was elevated on monocytes, whereas the density of CD49d was reduced on this population in FIP. Granulocytes of FIP cats displayed an increased expression of the α chain of Mac-1 (CD11b). These observations suggest that leukocytes from FIP patients show signs of systemic activation causing them to extravasate into surrounding tissues and ultimately contribute to pyogranuloma formation seen in FIP.

  12. The effect of biological sealants and adhesive treatments on matrix metalloproteinase expression during renal injury healing

    PubMed Central

    2017-01-01

    Background Renal injuries are relatively common in cases of abdominal trauma. Adhesives and sealants can be used to repair and preserve damaged organs. Using a rat model, this study explores the activity of different matrix metalloproteinases (MMP) during the healing of renal injuries treated by two biological adhesives (TachoSil and GelitaSpon) and a new synthetic elastic cyanoacrylate (Adhflex). Methods Renal traumatic injuries were experimentally induced in 90 male Wistar rats by a Stiefel Biopsy Punch in the anterior aspect of the left kidney. Animals were divided into five groups: 1, sham non-injured (n = 3); 2, non-treated standard punch injury (n = 6); 3, punch injury treated with TachoSil (n = 27); 4, punch injury treated with GelitaSpon (n = 27); and, 5, punch injury treated with Adhflex (n = 27). Wound healing was evaluated 2, 6, and 18 days after injury by determining the expression of MMPs, and the histopathological evolution of lesions. Findings Histologically, the wound size at 6 days post-injury was larger in Adhflex-treated samples than in the other treatments, but the scarring tissue was similar at 18 days post-injury. Only the MMPs subtypes 1, 2, 8, 9, and 13 were sufficiently expressed to be quantifiable. Both time since injury and treatment type had a significant influence on MMPs expression. Two days after injury, the expression of MMP8 and MMP9 was predominant. MMP2 expression was greater 6 days after injury. The Adhflex-treated group had a significantly higher MMPs expression than the other treatment groups at all healing stages. Conclusions All three sealant treatments induced almost similar expression of MMPs than untreated animals indicating a physiological healing process. Given that all renal trauma injuries must be considered emergencies, both biological and synthetic adhesives, such as Adhflex, should be considered as a treatment options. PMID:28494022

  13. Inhalation of ultrafine particles alters blood leukocyte expression of adhesion molecules in humans.

    PubMed

    Frampton, Mark W; Stewart, Judith C; Oberdörster, Günter; Morrow, Paul E; Chalupa, David; Pietropaoli, Anthony P; Frasier, Lauren M; Speers, Donna M; Cox, Christopher; Huang, Li-Shan; Utell, Mark J

    2006-01-01

    Ultrafine particles (UFPs; aerodynamic diameter < 100 nm) may contribute to the respiratory and cardiovascular morbidity and mortality associated with particulate air pollution. We tested the hypothesis that inhalation of carbon UFPs has vascular effects in healthy and asthmatic subjects, detectable as alterations in blood leukocyte expression of adhesion molecules. Healthy subjects inhaled filtered air and freshly generated elemental carbon particles (count median diameter approximately 25nm, geometric standard deviation approximately 1.6), for 2 hr, in three separate protocols: 10 microg/m3 at rest, 10 and 25 microg/m3 with exercise, and 50 microg/m3 with exercise. In a fourth protocol, subjects with asthma inhaled air and 10 microg/m3 UFPs with exercise. Peripheral venous blood was obtained before and at intervals after exposure, and leukocyte expression of surface markers was quantitated using multiparameter flow cytometry. In healthy subjects, particle exposure with exercise reduced expression of adhesion molecules CD54 and CD18 on monocytes and CD18 and CD49d on granulocytes. There were also concentration-related reductions in blood monocytes, basophils, and eosinophils and increased lymphocyte expression of the activation marker CD25. In subjects with asthma, exposure with exercise to 10 microg/m3 UFPs reduced expression of CD11b on monocytes and eosinophils and CD54 on granulocytes. Particle exposure also reduced the percentage of CD4+ T cells, basophils, and eosinophils. Inhalation of elemental carbon UFPs alters peripheral blood leukocyte distribution and expression of adhesion molecules, in a pattern consistent with increased retention of leukocytes in the pulmonary vascular bed.

  14. Differential effects of EGF and amphiregulin on adhesion molecule expression and migration of colon carcinoma cells.

    PubMed

    Solic, N; Davies, D E

    1997-08-01

    Epidermal growth factor (EGF) is a potent morphogen affecting cell shape and motility through regulation of adhesive interactions. We have characterized the morphological effects of EGF on GP2d and GP5d colon carcinoma cell lines and have compared the ability of the heparin-binding EGF receptor ligand amphiregulin (AR) to elicit the same effects. EGF induced a marked epithelial-mesenchymal transition in both cell lines. This effect was evident at 7 pM EGF and was associated with a reduction in cellular adherens junctions and diminished cell-cell contact; it was also associated with an increase in expression of alpha2-integrin as well as enhanced adhesion to the substratum and cell spreading. These changes in adhesion molecule expression were accompanied by enhanced migration on collagen. Blockade of cell growth with mitomycin C did not prevent the EGF-induced morphological change, showing that the mitogenic and morphogenic responses of the GP cells were separable. The phosphatidyl inositol (PI) 3-kinase inhibitor wortmannin inhibited basal proliferation but had no effect on the EGF-induced morphological change, further suggesting that the PI 3-kinase pathway was not involved in the morphogenic response of these cells. Amphiregulin stimulated proliferation of both cell lines, but could only elicit a modest morphological change if used at considerably higher doses or if growth was blocked with mitomycin C. In cells treated with 55 nM AR, alpha2-integrin expression was slightly increased; however, unlike the EGF case, adherens junctions remained intact. These differences in the ability of EGF and amphiregulin to affect cellular adhesion and migration may be significant factors influencing normal and tumor cell behavior.

  15. The coffee diterpene kahweol inhibits tumor necrosis factor-{alpha}-induced expression of cell adhesion molecules in human endothelial cells

    SciTech Connect

    Kim, Hyung Gyun; Kim, Ji Young; Hwang, Yong Pil; Lee, Kyung Jin; Lee, Kwang Youl; Kim, Dong Hee; Kim, Dong Hyun; Jeong, Hye Gwang . E-mail: hgjeong@chosun.ac.kr

    2006-12-15

    Endothelial cells produce adhesion molecules after being stimulated with various inflammatory cytokines. These adhesion molecules play an important role in the development of atherogenesis. Recent studies have highlighted the chemoprotective and anti-inflammatory effects of kahweol, a coffee-specific diterpene. This study examined the effects of kahweol on the cytokine-induced monocyte/human endothelial cell interaction, which is a crucial early event in atherogenesis. Kahweol inhibited the adhesion of TNF{alpha}-induced monocytes to endothelial cells and suppressed the TNF{alpha}-induced protein and mRNA expression of the cell adhesion molecules, VCAM-1 and ICAM-1. Furthermore, kahweol inhibited the TNF{alpha}-induced JAK2-PI3K/Akt-NF-{kappa}B activation pathway in these cells. Overall, kahweol has anti-inflammatory and anti-atherosclerotic activities, which occurs partly by down-regulating the pathway that affects the expression and interaction of the cell adhesion molecules on endothelial cells.

  16. Plakophilin 2 Affects Cell Migration by Modulating Focal Adhesion Dynamics and Integrin Protein Expression

    PubMed Central

    Koetsier, Jennifer L.; Amargo, Evangeline V.; Todorović, Viktor; Green, Kathleen J.; Godsel, Lisa M.

    2014-01-01

    Plakophilin 2 (PKP2), a desmosome component, modulates the activity and localization of the small GTPase RhoA at sites of cell–cell contact. PKP2 regulates cortical actin rearrangement during junction formation, and its loss is accompanied by an increase in actin stress fibers. We hypothesized that PKP2 may regulate focal adhesion dynamics and cell migration. Here we show that PKP2-deficient cells bind efficiently to the extracellular matrix, but upon spreading display total cell areas ~30% smaller than control cells. Focal adhesions in PKP2-deficient cells are ~2× larger and more stable than in control cells, and vinculin displays an increased time for fluorescence recovery after photobleaching. Furthermore, β4 and β1 integrin protein and mRNA expression is elevated in PKP2-silenced cells. Normal focal adhesion phenotypes can be restored in PKP2-null cells by dampening the RhoA pathway or silencing β1 integrin. However, integrin expression levels are not restored by RhoA signaling inhibition. These data uncover a potential role for PKP2 upstream of β1 integrin and RhoA in integrating cell–cell and cell–substrate contact signaling in basal keratinocytes necessary for the morphogenesis, homeostasis, and reepithelialization of the stratified epidermis. PMID:23884246

  17. Cellular Adhesion Gene SELP Is Associated with Rheumatoid Arthritis and Displays Differential Allelic Expression

    PubMed Central

    Petit-Teixeira, Elisabeth; Hugo Teixeira, Vitor; Steiner, Anke; Quente, Elfi; Wolfram, Grit; Scholz, Markus; Pierlot, Céline; Migliorini, Paola; Bombardieri, Stefano; Balsa, Alejandro; Westhovens, René; Barrera, Pilar; Radstake, Timothy R. D. J.; Alves, Helena; Bardin, Thomas; Prum, Bernard; Emmrich, Frank; Cornelis, François

    2014-01-01

    In rheumatoid arthritis (RA), a key event is infiltration of inflammatory immune cells into the synovial lining, possibly aggravated by dysregulation of cellular adhesion molecules. Therefore, single nucleotide polymorphisms of 14 genes involved in cellular adhesion processes (CAST, ITGA4, ITGB1, ITGB2, PECAM1, PTEN, PTPN11, PTPRC, PXN, SELE, SELP, SRC, TYK2, and VCAM1) were analyzed for association with RA. Association analysis was performed consecutively in three European RA family sample groups (Nfamilies = 407). Additionally, we investigated differential allelic expression, a possible functional consequence of genetic variants. SELP (selectin P, CD62P) SNP-allele rs6136-T was associated with risk for RA in two RA family sample groups as well as in global analysis of all three groups (ptotal = 0.003). This allele was also expressed preferentially (p<10−6) with a two- fold average increase in regulated samples. Differential expression is supported by data from Genevar MuTHER (p1 = 0.004; p2 = 0.0177). Evidence for influence of rs6136 on transcription factor binding was also found in silico and in public datasets reporting in vitro data. In summary, we found SELP rs6136-T to be associated with RA and with increased expression of SELP mRNA. SELP is located on the surface of endothelial cells and crucial for recruitment, adhesion, and migration of inflammatory cells into the joint. Genetically determined increased SELP expression levels might thus be a novel additional risk factor for RA. PMID:25147926

  18. Differential expression of cell adhesion molecules in the functional compartments of lymph nodes and tonsils

    PubMed Central

    Leite, R P; Carmo-Fonseca, M; Cabeçadas, J; Parreira, A; Parreira, L

    1995-01-01

    Aims—To analyse the topographical distribution of adhesion molecules involved in lymphocyte recirculation in human lymph nodes and tonsils. The study focused on the expression of LECAM-1 (CD62L), VLA-α4 (CD49d), VLA-β1 (CD29), LFA-1 αL (CD11a), LFA-β2 (CD18), VCAM-1 (CD106), ICAM-1 (CD54), and H-CAM (CD44). Methods—Reactive lymph nodes and palatine tonsils were studied using immunofluorescence methods with fluorescein isothiocyanate (FITC) labelled monoclonal antibodies directed against cell adhesion molecules. To investigate the expression patterns of these molecules in the T and B cell populations, double labelling experiments were performed using Texas Red labelled antibodies against CD2 or CD19, respectively. The images from each fluorochrome were then simultaneously analysed using a laser scanning confocal microscope. Results—LECAM-1, VLA-α4 and H-CAM were predominantly expressed by mantle zone B cells, VCAM-1 and ICAM-1 by germinal centre cells, most of which exhibited a reticular staining pattern suggestive of follicular dendritic cells, whereas LFA-1 αL and LFA-β2 were mainly found in extrafollicular and germinal centre T cells. All high endothelial venules expressed VLA-β1 and ICAM-1, whereas VCAM-1 was present in only a few, with variable intensity. Conclusions—The data show that all of these adhesion molecules are differentially distributed within the distinct functional microenvironments of both organs. The differences observed in the expression patterns among the B and T cells belonging to different compartments probably depend on the momentum of cell traffic, the stage of maturation/activation, as well as on their functional role in the immune response. Images PMID:16695989

  19. Neutrophil adhesion molecule expression during cardiopulmonary bypass: a comparative study of roller and centrifugal pumps.

    PubMed

    Macey, M G; McCarthy, D A; Trivedi, U R; Venn, G E; Chambers, D J; Brown, K A

    1997-09-01

    The purpose of this study was to determine whether adhesion molecules and markers of cell activation were preferentially increased on blood neutrophils during cardiopulmonary bypass (CPB) and whether such effects were influenced by the use of a roller pump or a centrifugal pump. Forty-six patients undergoing open heart surgery were randomly allocated into either the roller or centrifugal groups. Blood (1 ml volumes) was removed from arterial and venous lines immediately before and 1 h after the start of bypass. Whole blood samples were immunolabelled and flow cytometry used to measure the distribution and expression of the adhesion molecules CD11b, CD18, CD62L on neutrophils, monocytes and lymphocytes, in addition to CD64 on neutrophils and monocytes, and CD14 on monocytes. The expression of CD11b was significantly enhanced on neutrophils in arterial and venous samples from both the roller pump (mean 84% and 100% increase, respectively; p < 0.001) and centrifugal pump (mean 74% and 73% increase, respectively; p < 0.001) groups. Neutrophil L-selectin expression increased to a small but significant extent in arterial and venous samples from the centrifugal pump group (mean 16% increase; p < 0.001) and in venous samples from the roller pump group (mean 10% increase; p < 0.01). Neither the percentage of neutrophils bearing CD11b/CD18, CD62L and CD64, nor the expression of adhesion molecules on lymphocytes and monocytes were modified by 1 h of bypass. These results suggest that patients subjected to CPB with roller or centrifugal pumps are equally at risk to neutrophil activation that could lead to increased interaction of these cells with blood vessel walls.

  20. Multifunctional interleukin-1beta promotes metastasis of human lung cancer cells in SCID mice via enhanced expression of adhesion-, invasion- and angiogenesis-related molecules.

    PubMed

    Yano, Seiji; Nokihara, Hiroshi; Yamamoto, Akihiko; Goto, Hisatsugu; Ogawa, Hirohisa; Kanematsu, Takanori; Miki, Toyokazu; Uehara, Hisanori; Saijo, Yasuo; Nukiwa, Toshihiro; Sone, Saburo

    2003-03-01

    We examined whether interleukin-1 (IL-1), a multifunctional proinflammatory cytokine, progresses or regresses metastasis of lung cancer. Exogenous IL-1beta enhanced expression of various cytokines (IL-6, IL-8, and vascular endothelial growth factor (VEGF)) and intracellular adhesion molecule-1 (ICAM-1) by A549, PC14, RERF-LC-AI, and SBC-3 cells expressing IL-1 receptors. A549 cells transduced with human IL-1beta-gene with the growth-hormone signaling-peptide sequence (A549/IL-1beta) secreted a large amount of IL-1beta protein. Overexpression of IL-1beta resulted in augmentation of expression of the cytokines, ICAM-1, and matrix metalloproteinase-2 (MMP-2). A549/IL-1beta cells intravenously inoculated into severe combined immunodeficiency (SCID) mice distributed to the lung more efficiently and developed lung metastasis much more rapidly than did control A549 cells. Treatment of SCID mice with anti-IL-1beta antibody inhibited formation of lung metastasis by A549/IL-1beta cells. Moreover, A549/IL-1beta cells inoculated in the subcutis grew more rapidly, without necrosis, than did control A549 cells, which produced smaller tumors with central necrosis, suggesting involvement of angiogenesis in addition to enhanced binding in the high metastatic potential of A549/IL-1beta cells. Histological analyses showed that more host-cell infiltration, fewer apoptotic cells, more vascularization, and higher MMP activity were observed in tumors derived from A549/IL-1beta cells, compared with tumors derived from control A549 cells. These findings suggest that IL-1beta facilitates metastasis of lung cancer via promoting multiple events, including adhesion, invasion and angiogenesis.

  1. Titanium dioxide nanoparticles induce the expression of early and late receptors for adhesion molecules on monocytes.

    PubMed

    Rueda-Romero, Cristhiam; Hernández-Pérez, Guillermina; Ramos-Godínez, Pilar; Vázquez-López, Inés; Quintana-Belmares, Raúl Omar; Huerta-García, Elizabeth; Stepien, Ewa; López-Marure, Rebeca; Montiel-Dávalos, Angélica; Alfaro-Moreno, Ernesto

    2016-06-23

    There is growing evidence that exposure to titanium dioxide nanoparticles (TiO2 NPs) could be harmful. Previously, we have shown that TiO2 NPs induces endothelial cell dysfunction and damage in glial cells. Considering that inhaled particles can induce systemic effects and the evidence that nanoparticles may translocate out of the lungs, we evaluated whether different types of TiO2 NPs can induce the expression of receptors for adhesion molecules on monocytes (U937 cell line). We evaluated the role of reactive oxygen spices (ROS) on these effects. The expression of receptors for early (sLe(x) and PSGL-1) and late (LFA-1, VLA-4 and αVβ3) adhesion molecules was evaluated in U937 cells on a time course (3-24 h) using a wide range of concentrations (0.001-100 μg/mL) of three types of TiO2 NPs (<25 nm anatase, 50 nm anatase-rutile or < 100 nm anatase). Cells exposed to TNFα were considered positive controls, and unexposed cells, negative controls. In some experiments we added 10 μmolar of N-acetylcysteine (NAC) to evaluate the role of ROS. All tested particles, starting at a concentration of 0.03 μg/mL, induced the expression of receptors for early and late adhesion molecules. The largest increases were induced by the different molecules after 3 h of exposure for sLe(x) and PSGL-1 (up to 3-fold of the positive controls) and after 18 h of exposure for LFA-1, VLA-4 and αVβ3 (up to 2.5-fold of the positive controls). Oxidative stress was observed as early as 10 min after exposure, but the maximum peak was found after 4 h of exposure. Adhesion of exposed or unexposed monocytes to unexposed or exposed endothelial cells was tested, and we observed that monocytes cells adhere in similar amounts to endothelial cells if one of the two cell types, or both were exposed. When NAC was added, the expression of the receptors was inhibited. These results show that small concentrations of particles may activate monocytes that attach to endothelial cells. These

  2. Dynamic expression of the cell adhesion molecule fasciclin I during embryonic development in Drosophila.

    PubMed

    McAllister, L; Goodman, C S; Zinn, K

    1992-05-01

    A number of different cell surface glycoproteins expressed in the central nervous system (CNS) have been identified in insects and shown to mediate cell adhesion in tissue culture systems. The fasciclin I protein is expressed on a subset of CNS axon pathways in both grasshopper and Drosophila. It consists of four homologous 150-amino acid domains which are unrelated to other sequences in the current databases, and is tethered to the cell surface by a glycosyl-phosphatidylinositol linkage. In this paper we examine in detail the expression of fasciclin I mRNA and protein during Drosophila embryonic development. We find that fasciclin I is expressed in several distinct patterns at different stages of development. In blastoderm embryos it is briefly localized in a graded pattern. During the germ band extended period its expression evolves through two distinct phases. Fasciclin I mRNA and protein are initially localized in a 14-stripe pattern which corresponds to segmentally repeated patches of neuroepithelial cells and neuroblasts. Expression then becomes confined to CNS and peripheral sensory (PNS) neurons. Fasciclin I is expressed on all PNS neurons, and this expression is stably maintained for several hours. In the CNS, fasciclin I is initially expressed on all commissural axons, but then becomes restricted to specific axon bundles. The early commissural expression pattern is not observed in grasshopper embryos, but the later bundle-specific pattern is very similar to that seen in grasshopper. The existence of an initial phase of expression on all commissural bundles helps to explain the loss-of-commissures phenotype of embryos lacking expression of both fasciclin I and of the D-abl tyrosine kinase. Fasciclin I is also expressed in several nonneural tissues in the embryo.

  3. MICA Expression Is Regulated by Cell Adhesion and Contact in a FAK/Src-Dependent Manner

    PubMed Central

    Moncayo, Gerald; Lin, Da; McCarthy, Michael T.; Watson, Aleksandra A.; O’Callaghan, Christopher A.

    2017-01-01

    MICA is a major ligand for the NKG2D immune receptor, which plays a key role in activating natural killer (NK) cells and cytotoxic T cells. We analyzed NKG2D ligand expression on a range of cell types and could demonstrate that MICA expression levels were closely linked to cellular growth mode. While the expression of other NKG2D ligands was largely independent of cell growth mode, MICA expression was mainly found on cells cultured as adherent cells. In addition, MICA surface expression was reduced through increase in cell–cell contact or loss of cell–matrix adherence. Furthermore, we found that the reduction in MICA expression was modulated by focal adhesion kinase (FAK)/Src signaling and associated with increased susceptibility to NK cell-mediated killing. While the mechanisms of tumor immune evasion are not fully understood, the reduction of MICA expression following loss of attachment poises a potential way by which metastasizing tumor cells avoid immune detection. The role of FAK/Src in this process indicates a potential therapeutic approach to modulate MICA expression and immune recognition of tumor cells during metastasis. PMID:28154561

  4. [Expression of cell adhesion molecules in the maternal fetal period of human gestation].

    PubMed

    Vega-Sánchez, Rodrigo; de Jesús-Torres, Elizabeth; Arenas-Hernández, Marcia; Beltrán-Montoya, Jorge; Maida-Claros, Rolando; Estrada-Gutiérrez, Guadalupe; Vadillo-Ortega, Felipe

    2010-12-01

    The human labor is an inflammatory process invading leukocytes modulated by gestational tissues. The local increase of cell adhesion molecules (CAMs) promotes the permanence of these leukocytes in the coriodecidua. Gestational tissues express ICAM-1, while circulating leukocytes expressing its ligand Mac-1. To analyze, first, if the expression of CAMs in the fetal membranes is associated with progress of gestational age, and second, the expression of CAMs on circulating leukocytes in the uterus (placenta). original and closed study conducted at the Instituto Nacional de Perinatologia Isidro Espinosa de los Reyes (Mexico City). We included samples from healthy women between 15 and 44 years of age with term pregnancies (> or =37 weeks gestation). Real time PCR analysis showed that the expression of CAMs in the fetal membranes remained constant before labor. ICAM3 and ICAM1 tended to increase during labor, while ICAM2, VCAM1, SELE and SELP decrease with advancing gestational age. Placental leukocytes showed a clear increase in the expression of ITGAM (Mac-1) during labor. These results show that the maternal-fetal interface expresses a specific combination of CAMs during labor, including ICAM1, ICAM-3 and Mac-1. The expression of these molecules could promote the retention of leukocytes in the local tissues to modulate the local inflammatory microenvironment during human labor.

  5. Expression changes of nerve cell adhesion molecules L1 and semaphorin 3A after peripheral nerve injury

    PubMed Central

    He, Qian-ru; Cong, Meng; Chen, Qing-zhong; Sheng, Ya-feng; Li, Jian; Zhang, Qi; Ding, Fei; Gong, Yan-pei

    2016-01-01

    The expression of nerve cell adhesion molecule L1 in the neuronal growth cone of the central nervous system is strongly associated with the direction of growth of the axon, but its role in the regeneration of the peripheral nerve is still unknown. This study explored the problem in a femoral nerve section model in rats. L1 and semaphorin 3A mRNA and protein expressions were measured over the 4-week recovery period. Quantitative polymerase chain reaction showed that nerve cell adhesion molecule L1 expression was higher in the sensory nerves than in motor nerves at 2 weeks after injury, but vice versa for the expression of semaphorin 3A. Western blot assay results demonstrated that nerve cell adhesion molecule L1 expression was higher in motor nerves than in the sensory nerves at the proximal end after injury, but its expression was greater in the sensory nerves at 2 weeks. Semaphorin 3A expression was higher in the motor nerves than in the sensory nerves at 3 days and 1 week after injury. Nerve cell adhesion molecule L1 and semaphorin 3A expressions at the distal end were higher in the motor nerves than in the sensory nerves at 3 days, 1 and 2 weeks. Immunohistochemical staining results showed that nerve cell adhesion molecule L1 expression at the proximal end was greater in the sensory nerves than in the motor nerves; semaphorin 3A expression was higher in the motor nerves than in the sensory nerves at 2 weeks after injury. Taken together, these results indicated that nerve cell adhesion molecules L1 and semaphorin 3A exhibited different expression patterns at the proximal and distal ends of sensory and motor nerves, and play a coordinating role in neural chemotaxis regeneration. PMID:28197202

  6. Iron sucrose accelerates early atherogenesis by increasing superoxide production and upregulating adhesion molecules in CKD.

    PubMed

    Kuo, Ko-Lin; Hung, Szu-Chun; Lee, Tzong-Shyuan; Tarng, Der-Cherng

    2014-11-01

    High-dose intravenous iron supplementation is associated with adverse cardiovascular outcomes in patients with CKD, but the underlying mechanism is unknown. Our study investigated the causative role of iron sucrose in leukocyte-endothelium interactions, an index of early atherogenesis, and subsequent atherosclerosis in the mouse remnant kidney model. We found that expression levels of intracellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) and adhesion of U937 cells increased in iron-treated human aortic endothelial cells through upregulated NADPH oxidase (NOx) and NF-κB signaling. We then measured mononuclear-endothelial adhesion and atherosclerotic lesions of the proximal aorta in male C57BL/6 mice with subtotal nephrectomy, male apolipoprotein E-deficient (ApoE(-/-)) mice with uninephrectomy, and sham-operated mice subjected to saline or parenteral iron loading. Iron sucrose significantly increased tissue superoxide production, expression of tissue cell adhesion molecules, and endothelial adhesiveness in mice with subtotal nephrectomy. Moreover, iron sucrose exacerbated atherosclerosis in the aorta of ApoE(-/-) mice with uninephrectomy. In patients with CKD, intravenous iron sucrose increased circulating mononuclear superoxide production, expression of soluble adhesion molecules, and mononuclear-endothelial adhesion compared with healthy subjects or untreated patients. In summary, iron sucrose aggravated endothelial dysfunction through NOx/NF-κB/CAM signaling, increased mononuclear-endothelial adhesion, and exacerbated atherosclerosis in mice with remnant kidneys. These results suggest a novel causative role for therapeutic iron in cardiovascular complications in patients with CKD.

  7. Leukocyte trafficking-associated vascular adhesion protein 1 is expressed and functionally active in atherosclerotic plaques

    PubMed Central

    Silvola, Johanna M. U.; Virtanen, Helena; Siitonen, Riikka; Hellberg, Sanna; Liljenbäck, Heidi; Metsälä, Olli; Ståhle, Mia; Saanijoki, Tiina; Käkelä, Meeri; Hakovirta, Harri; Ylä-Herttuala, Seppo; Saukko, Pekka; Jauhiainen, Matti; Veres, Tibor Z.; Jalkanen, Sirpa; Knuuti, Juhani; Saraste, Antti; Roivainen, Anne

    2016-01-01

    Given the important role of inflammation and the potential association of the leukocyte trafficking-associated adhesion molecule vascular adhesion protein 1 (VAP-1) with atherosclerosis, this study examined whether functional VAP-1 is expressed in atherosclerotic lesions and, if so, whether it could be targeted by positron emission tomography (PET). First, immunohistochemistry revealed that VAP-1 localized to endothelial cells of intra-plaque neovessels in human carotid endarterectomy samples from patients with recent ischemic symptoms. In low-density lipoprotein receptor-deficient mice expressing only apolipoprotein B100 (LDLR−/−ApoB100/100), VAP-1 was expressed on endothelial cells lining inflamed atherosclerotic lesions; normal vessel walls in aortas of C57BL/6N control mice were VAP-1-negative. Second, we discovered that the focal uptake of VAP-1 targeting sialic acid-binding immunoglobulin-like lectin 9 based PET tracer [68Ga]DOTA-Siglec-9 in atherosclerotic plaques was associated with the density of activated macrophages (r = 0.58, P = 0.022). As a final point, we found that the inhibition of VAP-1 activity with small molecule LJP1586 decreased the density of macrophages in inflamed atherosclerotic plaques in mice. Our results suggest for the first time VAP-1 as a potential imaging target for inflamed atherosclerotic plaques, and corroborate VAP-1 inhibition as a therapeutic approach in the treatment of atherosclerosis. PMID:27731409

  8. Expression of endothelial adhesion molecules in the alveolar ridge mucosa, gingiva and periimplant mucosa.

    PubMed

    Zitzmann, N U; Berglundh, T; Marinello, C P; Lindhe, J

    2002-06-01

    The purpose of this study was to analyze the expression of adhesion molecules on endothelial cells in the alveolar ridge mucosa, the gingiva and the periimplant mucosa in humans. Twelve partially edentulous subjects were included in the study. In each subject, one soft tissue biopsy was harvested from the edentulous alveolar ridge mucosa, one from a tooth site and one from an implant site. After 3 weeks of undisturbed plaque accumulation, an additional biopsy was obtained from one tooth and one implant site in each subject. The tissue samples were snap frozen and prepared for immunohistochemical analysis. In the alveolar ridge mucosa, smaller proportions of endothelial cells expressing ICAM-1, ELAM-1 and VCAM-1 were observed than in the gingiva. ELAM-1-positive cells occurred in lower numbers than in periimplant mucosa. After 21 days of plaque accumulation, ELAM-1 was increased in tooth sites, but decreased in periimplant mucosa. The results of the present study indicated that the proportions of activated endothelial cells and the extravasation of leukocytes is larger in gingiva and periimplant mucosa than in alveolar ridge mucosa. This might be due to the less permeable keratinized epithelial layer in the edentulous ridge mucosa, which offers proper protection against microbial pathogens. The greater expression of endothelial cell adhesion molecules during experimental gingivitis, compared to periimplant mucositis, may reflect its longer history of repeated antigenic assaults.

  9. Activated Leukocyte Cell Adhesion Molecule Expression and Shedding in Thyroid Tumors

    PubMed Central

    Miccichè, Francesca; Da Riva, Luca; Fabbi, Marina; Pilotti, Silvana; Mondellini, Piera; Ferrini, Silvano; Canevari, Silvana; Pierotti, Marco A.; Bongarzone, Italia

    2011-01-01

    Activated leukocyte cell adhesion molecule (ALCAM, CD166) is expressed in various tissues, cancers, and cancer-initiating cells. Alterations in expression of ALCAM have been reported in several human tumors, and cell adhesion functions have been proposed to explain its association with cancer. Here we documented high levels of ALCAM expression in human thyroid tumors and cell lines. Through proteomic characterization of ALCAM expression in the human papillary thyroid carcinoma cell line TPC-1, we identified the presence of a full-length membrane-associated isoform in cell lysate and of soluble ALCAM isoforms in conditioned medium. This finding is consistent with proteolytically shed ALCAM ectodomains. Nonspecific agents, such as phorbol myristate acetate (PMA) or ionomycin, provoked increased ectodomain shedding. Epidermal growth factor receptor stimulation also enhanced ALCAM secretion through an ADAM17/TACE-dependent pathway. ADAM17/TACE was expressed in the TPC-1 cell line, and ADAM17/TACE silencing by specific small interfering RNAs reduced ALCAM shedding. In addition, the CGS27023A inhibitor of ADAM17/TACE function reduced ALCAM release in a dose-dependent manner and inhibited cell migration in a wound-healing assay. We also provide evidence for the existence of novel O-glycosylated forms and of a novel 60-kDa soluble form of ALCAM, which is particularly abundant following cell stimulation by PMA. ALCAM expression in papillary and medullary thyroid cancer specimens and in the surrounding non-tumoral component was studied by western blot and immunohistochemistry, with results demonstrating that tumor cells overexpress ALCAM. These findings strongly suggest the possibility that ALCAM may have an important role in thyroid tumor biology. PMID:21364949

  10. Retinoic acid receptor gamma impacts cellular adhesion, Alpha5Beta1 integrin expression and proliferation in K562 cells.

    PubMed

    Kelley, Melissa D; Phomakay, Raynin; Lee, Madison; Niedzwiedz, Victoria; Mayo, Rachel

    2017-01-01

    The interplay between cellular adhesion and proliferation is complex; however, integrins, particularly the α5β1 subset, play a pivotal role in orchestrating critical cellular signals that culminate in cellular adhesion and growth. Retinoids modify the expression of a variety of adhesive/proliferative signaling proteins including α5β1 integrins; however, the role of specific retinoic acid receptors involved in these processes has not been elucidated. In this study, the effect of all-trans-retinoic acid receptor (RAR) agonists on K562 cellular adhesion, proliferation, and α5β1 integrin cell surface expression was investigated. RARγ agonist exposure increased K562 cellular adhesion to RGD containing extracellular matrix proteins fibronectin and FN-120 in a time- and concentration dependent manner, while RARα or RARβ agonist treatment had no effect on cellular adhesion. Due to the novel RARγ- dependent cellular adhesion response exhibited by K562 cells, we examined α5 and β1 integrin subunit expression when K562 cells were exposed to retinoid agonists or vehicle for 24, 48, 72 or 96 hours. Our data demonstrates no differences in K562 cell surface expression of the α5 integrin subunit when cells were exposed to RARα, RARβ, or RARγ agonists for all time points tested. In contrast, RARγ agonist exposure resulted in an increase in cell surface β1 integrin subunit expression within 48 hours that was sustained at 72 and 96 hours. Finally, we demonstrate that while exposure to RARα or RARβ agonists have no effect on K562 cellular proliferation, the RARγ agonist significantly dampens K562 cellular proliferation levels in a time- and concentration- dependent manner. Our study is the first to report that treatment