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Intercellular Adhesion Molecule (intercellular + adhesion_molecule)
Selected AbstractsAssociation between recipient ICAM-1 K469 allele and renal allograft acute rejectionINTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 1 2008N. Tajik Summary Intercellular adhesion molecule 1 (ICAM-1) genetic polymorphisms (G241R and K469E) have been implicated in several autoimmune and inflammatory conditions. Investigating a sample of living-unrelated donor (LURD) kidney transplant pairs, we revealed an association between recipient K469 allele (P = 0.013) and K/K genotype (P = 0.042) with renal allograft acute rejection. [source] Relationship between protective effects of rosiglitazone on endothelium and endogenous nitric oxide synthase inhibitor in streptozotocin-induced diabetic rats and cultured endothelial cellsDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 2 2007Shan Wang Abstract Background Previous investigations have indicated that the level of asymmetric dimethylarginine (ADMA) is increased in diabetic patients and animals, and rosiglitazone has a protective effect on the endothelium. In the present study, we tested the relationship between protective effects of rosiglitazone and ADMA in streptozotocin (STZ)-induced diabetic rats and cultured endothelial cells. Methods Blood samples were collected from carotid artery. Vasodilator responses to acetylcholine (ACh) in the isolated aortic rings were measured, and serum concentrations of glucose, lipid, nitrite/nitrate, ADMA and tumour necrosis factor-, (TNF-,) were determined. Cultured endothelial cells were treated with ADMA, and the concentrations of intercellular adhesion molecule (ICAM-1), TNF-,, and the activity of nuclear factor-,B (NF-,B) were determined. Results Vasodilator responses to ACh were decreased markedly and the serum concentrations of TNF-,, nitrite/nitrate and ADMA were increased significantly in diabetic rats. Rosiglitazone (3, 10 or 30 mg/kg) produced a significant reduction of the inhibition of vasodilator responses to ACh, but had no effect on the serum concentrations of glucose, lipid, nitrite/nitrate and ADMA in diabetic rats. ADMA (30 µM) significantly increased the activity of NF-,B and elevated the levels of ICAM-1 and TNF-,, and pre-treatment with rosiglitazone (10 or 30 µM) markedly inhibited the increased activity of NF-,B and reduced the elevated levels of TNF-, and ICAM-1 induced by ADMA in cultured endothelial cells. Conclusions Rosiglitazone improves endothelial function in diabetic rats, which is related to the reduction of the inflammatory response induced by ADMA. Copyright © 2006 John Wiley & Sons, Ltd. [source] RANTES stimulates inflammatory cascades and receptor modulation in murine astrocytesGLIA, Issue 1 2002Yi Luo Abstract Cultured mouse astrocytes respond to the CC chemokine RANTES by production of chemokine and cytokine transcripts. Stimulation of astrocytes with 1 nM RANTES or 3,10 nM of the structurally related chemokines (eotaxin, macrophage inflammatory protein-1, and -, [MIP-1,, MIP-1,]) induced transcripts for KC, monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-, (TNF-,), MIP-1,, MIP-2, and RANTES in a chemokine and cell-specific fashion. Synthesis of chemokine (KC and MCP-1) and cytokine (TNF-,) proteins was also demonstrated. RANTES-mediated chemokine synthesis was specifically inhibited by pertussis toxin, indicating that G-protein-coupled chemokine receptors participated in astrocyte signaling. Astrocytes expressed CCR1 and CCR5 (the redundant RANTES receptors). Astrocytes derived from mice with targeted mutations of either CCR1 or CCR5 respond after RANTES stimulation, suggesting multiple chemokine receptors may separately mediate RANTES responsiveness in astrocytes. Preliminary data suggest activation of the MAP kinase pathway is also critical for RANTES-mediated signaling in astrocytes. Treatment with RANTES specifically modulated astrocyte receptors upregulating intercellular adhesion molecule 1 (ICAM-1) and downregulating CX3CR1 expression. Thus, after chemokine treatment, astrocytes release proinflammatory mediators and reprogram their surface molecules. The combined effects of RANTES may serve to amplify inflammatory responses within the central nervous system. GLIA 39:19,30, 2002. © 2002 Wiley-Liss, Inc. [source] Enhanced expression of B7-1, B7-2, and intercellular adhesion molecule 1 in sinusoidal endothelial cells by warm ischemia/reperfusion injury in rat liverHEPATOLOGY, Issue 4 2001Naosuke Kojima To elucidate a role of costimulatory molecule and cell adhesion molecule in hepatic ischemia/reperfusion injury, we examined an alteration in B7-1 (CD80), B7-2 (CD86), and intercellular adhesion molecule 1 (ICAM-1; CD54) expression in the rat liver after warm ischemia/reperfusion injury. To induce hepatic warm ischemia in a rat model, both portal vein and hepatic artery entering the left-lateral and median lobes were occluded by clamping for 30 minutes or 60 minutes, and then reperfused for 24 hours. B7-1, B7-2, and ICAM-1 expressions in the liver were analyzed by immunofluorescence staining and real-time reverse transcription polymerase chain reaction (RT-PCR). Although B7-1 and B7-2 expressions were at very low levels in the liver tissues from normal or sham-operated control rats, both B7-1 and B7-2 expressions were enhanced at protein and messenger RNA (mRNA) levels in the affected, left lobes after warm ischemia/reperfusion. ICAM-1 protein and mRNA were constitutively expressed in the liver of normal and sham-operated control rats, and further up-regulated after warm ischemia/reperfusion. Localization of increased B7-1, B7-2, and ICAM-1 proteins, as well as von Willebrand factor as a marker protein for endothelial cells, was confined by immunofluorescence staining to sinusoidal endothelial cells in hepatic lobules. Data from quantitative real-time RT-PCR analysis revealed that B7-1 and B7-2 mRNA levels were elevated in hepatic lobes after warm ischemia/reperfusion (5.13- and 52.9-fold increase, respectively), whereas ICAM-1 mRNA expression was rather constitutive but further enhanced by warm ischemia/reperfusion (4.24-fold increase). These results suggest that hepatic sinusoidal endothelial cells play a pivotal role as antigen-presenting cells by expressing B7-1 and B7-2 in warm hepatic ischemia/reperfusion injury, and that B7-1 and/or B7-2 might be the primary target to prevent early rejection and inflammatory reactions after hepatic ischemia/reperfusion injury associated with liver transplantation. [source] Plant sterol guggulsterone inhibits nuclear factor-,B signaling in intestinal epithelial cells by blocking I,B kinase and ameliorates acute murine colitisINFLAMMATORY BOWEL DISEASES, Issue 12 2006Jae Hee Cheon MD Abstract Background/Aims: The plant sterol guggulsterone has been shown to have anti-inflammatory properties. It remains unknown, however, whether guggulsterone is effective for the treatment of inflammatory bowel disease (IBD). Therefore, we investigated anti-inflammatory effects of guggulsterone on intestinal epithelial cells (IEC) and on experimental murine colitis models and elucidated its molecular mechanisms. Methods: Human Caco-2 cells and rat non-transformed IEC-18 cells were stimulated with interleukin (IL)-1, or lipopolysaccharide (LPS) with or without guggulsterone. The effects of guggulsterone on nuclear factor (NF)-,B signaling in IEC were examined by intercellular adhesion molecule (ICAM)-1 real-time reverse-transcription polymerase chain reaction, NF-,B transcriptional activity assay, Western blotting for I,B phosphorylation/degradation, electrophoretic mobility shift assay, and in vitro I,B kinase (IKK) assay. For in vivo study, dextran sulfate sodium (DSS)-treated mice were fed with or without guggulsterone. Colitis was quantified by disease activity index and evaluation of macroscopic and microscopic findings. Phosphorylation of I,B and IKK in colon mucosa was assessed by Western blotting and immunohistochemistry. Results: Guggulsterone significantly inhibited LPS- or IL-1,-induced ICAM-1 gene expression, NF-,B transcriptional activity, I,B phosphorylation/degradation, and NF-,B DNA binding activity in IEC. Moreover, guggulsterone strongly blocked IKK activity. Administration of guggulsterone significantly reduced the severity of DSS-induced murine colitis as assessed by clinical disease activity score, colon length, and histology. Furthermore, tissue upregulation of I,B and IKK phosphorylation induced by DSS was attenuated in guggulsterone-treated mice. Conclusion: Guggulsterone blocks NF-,B signaling pathway by targeting IKK complex in IEC and attenuates DSS-induced acute murine colitis, which suggests that guggulsterone could be an attractive therapeutic option in the treatment of IBD. [source] Expression of CD66a in multiple myelomaJOURNAL OF CLINICAL LABORATORY ANALYSIS, Issue 2 2002Yukihiko Satoh Abstract CD66a is a member of the carcinoembryonic antigen family and has been suggested to function as an intercellular adhesion molecule and cell growth regulator. Expression of CD66a in myeloma cells was examined with mAb TS135 against CD66a transfectants of murine-transformed fibroblasts. The reactivity of mAb TS135 with CD66a, CD66c, and CD66e was revealed. CD66a in myeloma cells was considered to be detectable with this mAb, since CD66c and CD66e are not expressed in them. CD66a was detected in three myeloma cell lines and an IgM-producing B-cell line. In clinical bone marrow specimens, including 18 multiple myeloma, two primary macroglobulinemia, and a case of CLL-like chronic lymphoproliferation with monoclonal IgG production, CD66a and three conventional myeloma cell markers (PCA-1, CD38, and CD56) were examined by indirect immunofluorescence assay. The results showed that 18 out of 21 cases (86%) were CD66a+, and PCA-1 showed the highest correlation with CD66a among conventional markers. Primary macroglobulinemia and chronic lymphoproliferation were also CD66a+. Two-dimensional flow cytometry with mAbs TS135 and CD38 confirmed the reactivity of TS135 with myeloma cells in those bone marrow specimens. The findings suggest that CD66a is expressed in multiple myeloma with high frequency. J. Clin. Lab. Anal. 16:79,85, 2002. © 2002 Wiley-Liss, Inc. [source] Expression of intercellular adhesion molecule (ICAM)-1 or ICAM-2 is critical in determining sensitivity of pancreatic cancer cells to cytolysis by human ,,-T cells: Implications in the design of ,,-T-cell-based immunotherapies for pancreatic cancerJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 5 2009Zhiyong Liu Abstract Background and Aims:, ,,-T cells can recognize and kill malignant cells, particularly those of epithelial origin, through mechanisms which do not require the recognition of tumor-specific antigens (innate immune response). This natural ability of ,,-T cells to kill tumor cells in a tumor antigen-independent manner provides a strong rationale for developing clinical trials designed to exploit the innate antitumor properties of ,,-T cells. Methods:,In vitro studies were carried out to asses the sensitivity of pancreatic cancer cells (MIA PaCa2, BxPC-3, PANC-1) to killing by ex vivo expanded human ,,-T cells. Results:, The capacity of ,,-T cells to bind to as well as to kill pancreatic cancer cells correlated with the degree of surface expression of key intercellular adhesion molecules (ICAM) present on pancreatic cancer cells. Moreover, pancreatic cancer cells expressing neither ICAM-1 nor ICAM-2 were bound poorly by ,,-T cells and were found to be resistant to ,,-T-cell killing. However, upon transfection of resistant cells with ICAM-1 or ICAM-2, ,,-T cells were then able to bind to and subsequently kill these cells. Conclusion:,In vitro, the expression of ICAM-1 or ICAM-2 on human pancreatic cancer cells is critically important in determining the extent to which these cells are sensitive to killing by human ,,-T cells. Accordingly, in ongoing and future clinical studies using ,,-T cells for the treatment of a variety of epithelial-derived solid tumors,including pancreatic cancer,interventions intended to modulate ICAM expression on tumor cells may become important adjuncts to ,,-T-cell-based immunotherapies. [source] Tumour necrosis factor-alpha plasma level in patients with type 1 diabetes mellitus and its association with glycaemic control and cardiovascular risk factorsJOURNAL OF INTERNAL MEDICINE, Issue 1 2000M. Lechleitner Abstract. Lechleitner M, Koch T, Herold M, Dzien A, Hoppichler F (University of Innsbruck, Medical Centre Hentschelhof, Innsbruck, and Hospital Barmherzige Brüder, Salzburg, Austria). tumour necrosis factor-alpha plasma level in patients with type 1 diabetes mellitus and its association with glycaemic control and cardiovascular risk factors. J Intern Med 2000: 248: 67,76. Objectives. Diabetic patients reveal a significant increase in their cardiovascular risk. Beside glycaemic control and management of established risk factors, determination of cytokines, like serum levels of tumour necrosis factor-alpha (TNF-,), might offer a tool to determine patients at high risk. The cytokine TNF-, reveals a complex relationship with diabetes. It is involved in beta-cell damage leading to type 1 diabetes, causes insulin resistance associated with obesity and is of influence in the formation of atherosclerotic vascular lesions. We were interested in the possible association of this cytokine with metabolic control and cardiovascular risk factors in patients with type 1 diabetes. Design and Subjects. TNF-, plasma levels were determined in 44 outdoor patients (15 women, 29 men) with type 1 diabetes mellitus (mean duration 11.2 ± 8.7 years) and in 24 healthy controls by use of a solid phase enzyme amplified sensitivity immunoassay (TNF-,elisa, Biosource Fleurus, Belgium). None of our study participants suffered from inflammatory or other concurrent diseases. Relationships between variables were evaluated by non-parametric Spearman correlation coefficients. Results. TNF-, plasma levels were significantly higher in diabetic patients (19.3 ± 7.5 pg mL,1) than in non-diabetic subjects (11.1 ± 5.8 pg mL,1; P < 0.023), and revealed a significant positive correlation with glycated haemoglobin (HbA1c) (r = 0.43; P < 0.004) and fructosamine (r = 0.31; P < 0.049) values, and a negative correlation with HDL cholesterol (r = ,0.36; P < 0.018) and apoAI-levels (r = ,0.37; P < 0.015). These relationships could be observed in patients with a duration of diabetes for more than 5 years, as well as in patients with a shorter duration of diabetes. In the male group, TNF-, plasma levels revealed a significant positive correlation with plasma levels of thiobarbituric acid reacting substances (r = 0.61; P < 0.001). Plasma levels of thiobarbituric acid reacting substances showed a positive correlation with the duration of diabetes (r = 0.58; P < 0.008), as well as with the serum levels of the vascular adhesion molecules intercellular adhesion molecule (ICAM) (r = 0.34; P < 0.051) and vascular cell adhesion molecule (VCAM) (r = 0.30; P < 0.052). Conclusions. Our data indicate that TNF-, plasma levels are increased in type 1 diabetes mellitus and reveal a significant association with metabolic long-term control parameters, HbA1c and fructosamine for glycaemic control, and HDL cholesterol for triglyceride metabolism, as well with lipid peroxidation. [source] Sirtinol attenuates hepatic injury and pro-inflammatory cytokine production following trauma-hemorrhage in male Sprague,Dawley ratsACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 5 2008F.-C. LIU Background: Although studies have demonstrated that sirtinol administration following adverse circulatory conditions is known to be protective, the mechanism by which sirtinol produces the salutary effects remains unknown. We hypothesized that sirtinol administration in male rats following trauma-hemorrhage decreases cytokine production and protects against hepatic injury. Methods: Male Sprague,Dawley rats underwent trauma-hemorrhage (mean blood pressure 40 mmHg for 90 min, then resuscitation). A single dose of sirtinol (1 mg/kg of body weight) or vehicle was administered intravenously during resuscitation. Twenty-four hours thereafter, tissue myeloperoxidase (MPO) activity (a marker of neutrophil sequestration), cytokine-induced neutrophil chemoattractant (CINC)-1, CINC-3, intercellular adhesion molecule (ICAM)-1, and interleukin (IL)-6 levels in the liver and plasma alanine aminotransferase (ALT) concentrations were measured (n=6 Sprague,Dawley rats/group). Results: Trauma-hemorrhage increased hepatic MPO activity, CINC-1, CINC-3, ICAM-1, and IL-6 levels and plasma ALT concentrations. These parameters were significantly improved in the sirtinol-treated rats subjected to trauma-hemorrhage. Conclusion: The salutary effects of sirtinol administration on attenuation of hepatic injury following trauma-hemorrhage are, at least in part, related to reduction of pro-inflammatory mediators. [source] Plasma hemostatic factors and endothelial markers in four racial/ethnic groups: the MESA studyJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 12 2006P. L. LUTSEY Summary.,Background:,Hemostatic factors and endothelial markers may play some role in racial/ethnic differences in cardiovascular disease (CVD) rates. However, little information exists on hemostatic factors and endothelial markers across racial/ethnic groups. Objectives:,To describe, in four American racial/ethnic groups (Caucasian, Black, Hispanic, and Chinese), mean levels of selected hemostatic factors and endothelial markers. Patients and methods:,Multi-ethnic Study of Atherosclerosis baseline data were used (participant age: 45,84 years). Sex-specific analysis of covariance models, and t -tests for pairwise comparisons, were used to compare means of factors and markers. Adjustments were made for demographics and traditional CVD risk factors. Differences were significant at P < 0.05. Results:,Blacks had the highest levels of factor VIII, D-Dimer, plasmin,antiplasmin (PAP), and von Willebrand factor, among the highest levels of fibrinogen and E-selectin (women only), but among the lowest levels of intercellular adhesion molecule 1 (ICAM-1), and, in men, the lowest levels of plasminogen activator inhibitor-1 (PAI-1). Whites and Hispanics tended to have intermediate levels of factors and markers, although they had the highest levels of ICAM-1, and Hispanics had the highest mean levels of fibrinogen and E-selectin (women only). Chinese participants had among the highest levels of PAI-1, but the lowest, or among the lowest, of all other factors and markers. No soluble thrombomodulin differences were observed. Conclusions:,In this large cohort, hemostatic factor and endothelial marker mean levels varied by race/ethnicity, even after adjustment for traditional CVD risk factors. [source] ICAM-1 expressed on hepatic stellate cells plays an important role in immune regulationMICROSURGERY, Issue 4 2007Zhenyu Yin M.D. The authors have demonstrated a strong T-cell inhibitory activity of hepatic stellate cells (HSC), which may participate in the establishment of hepatic tolerance. The underlying mechanism is not completely understood. This study showed that intercellular adhesion molecule 1 (ICAM-1) was constitutively expressed on HSC, and up-regulated upon activation. ICAM-1 knockout mice was used to analyze the role of ICAM-1 expressed on HSC, and showed that deficiency in ICAM-1 expression partially reverses HSC immune inhibitory activity both in vitro and in vivo, but did not significantly affect their capacity to induce T-cell apoptosis. © 2007 Wiley-Liss, Inc. Microsurgery 2007. [source] Differential effects of five Aggregatibacter actinomycetemcomitans strains on gingival epithelial cellsMOLECULAR ORAL MICROBIOLOGY, Issue 6 2008T. Shimada Introduction:, We investigated gingival epithelial cell proliferation and expression of interleukin-8 (IL-8) and intercellular adhesion molecule 1 (ICAM-1) in response to Aggregatibacter actinomycetemcomitans serotypes a, b, and c. Methods:, Human gingival cells (Ca9-22) were cultured in bacterial extracts prepared from five strains of A. actinomycetemcomitans: ATCC 43717 (serotype a); ATCC 29524, ATCC 29522, and ATCC 43718 (all serotype b); and ATCC 43719 (serotype c). Results:, In bacterial extracts of ATCC 29522, cell growth was significantly impaired, while the expression of IL-8 and ICAM-1 was significantly increased. The level of induction in response to the other strains was minimal. Conclusion:, Our results indicate that the five strains of A. actinomycetemcomitans have distinct effects on the abilities of human gingival epithelial cells to proliferate and to produce proinflammatory factors. [source] Adhesion molecule expression in experimental myositisMUSCLE AND NERVE, Issue 3 2002Tomoko Ito MD Abstract Experimental allergic myositis (EAM) in Lewis rats, induced with partially purified myosin, is regarded as a model of human polymyositis. To clarify the role of adhesion molecules in the pathogenesis of EAM in Lewis rats, we investigated intramysial expressions of the intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1, and the serum level of soluble ICAM-1 in EAM rats. All the EAM rat muscles had scattered inflammatory foci, as well as cell infiltration and necrosis, by week 4 after the initial immunization (i.e., day 0 after the last immunization). As compared with the control muscles, ICAM-1 and VCAM-1 were strongly expressed immunohistochemically in the endothelium of vessels in the endomysium and perimysium, and to lesser extents in the inflammatory infiltrates and on the sarcolemma of nonnecrotic muscle fibers adjacent to the inflammatory infiltrates or invaded muscle fibers. ICAM-1 in the muscle extracts and sera from EAM rats increased on each test day, as compared with extracts from the normal controls. The values peaked on day 0 after the last immunization, then gradually decreased with time. ICAM-1 elevations in the muscle extracts were correlated with the percent of sections that had inflammatory lesions (P = 0.032) and the histological scores (P = 0.005) on day 0, whereas there was no significance on days 3 and 7. These findings suggest that the adhesion molecules ICAM-1 and VCAM-1 increase in the early stage of EAM, and function in the initiation of the inflammatory process of myositis. © 2002 Wiley Periodicals, Inc. Muscle Nerve 25: 000,000, 2002 [source] Endothelial Cell Calpain Activity Facilitates Lymphocyte DiapedesisAMERICAN JOURNAL OF TRANSPLANTATION, Issue 11 2005Amer M. Hussain Lymphocyte infiltration of tissue is a cardinal feature of solid-organ allograft rejection. Vascular endothelial cells (EC) participate in lymphocyte recruitment through the display of adhesion molecules and chemokines to promote leukocyte extravasation. Moreover, EC reorganize the cytoskeleton and cytoskeleton-associated structures during leukocyte diapedesis. We examined the role of EC (Ca+2)i and the calcium-sensitive protease, calpain, during lymphocyte diapedesis through a human EC monolayer under physiologic shear stress in vitro. We observed that lymphocyte transendothelial migration (TEM) was inhibited by chelating EC cytosolic calcium, or depleting EC endoplasmic reticulum calcium stores by inhibition of the endoplasmic reticulum Ca ATPase. Further, inhibition of EC phospholiase C also decreased lymphocyte TEM. We determined that EC constitutively exhibit calpain activity, using fluorescence generation from a calpain substrate to report calpain activity in individual live cells. Moreover, EC adjacent to a transmigrating lymphocyte showed increased calpain activity. Further, lymphocyte TEM was inhibited by agents that block calpain activity. Inhibition of lymphocyte TEM occurs at the lumenal EC surface and correlates with impaired development of intercellular adhesion molecule 1 (ICAM-1)-rich docking structures by the EC. We conclude EC calcium and calpain activity facilitates lymphocyte TEM, and participates in the assembly of the docking structure. [source] Synovial tissue heterogeneity in rheumatoid arthritis in relation to disease activity and biomarkers in peripheral blood,ARTHRITIS & RHEUMATISM, Issue 6 2010Lisa G. M. van Baarsen Objective To investigate the clinical relevance of synovial tissue subtypes in rheumatoid arthritis (RA) and to search for peripheral blood (PB) markers that may serve as biomarkers for tissue subtypes. Methods Gene expression analysis using complementary DNA microarrays was applied on paired synovial tissue biopsy and PB samples obtained from 17 RA patients. Molecular tissue subtypes were correlated with histologic parameters (CD3, CD22, CD38, CD68, CD163, tumor necrosis factor ,, intercellular adhesion molecule 1, vascular cell adhesion molecule, and E-selectin), disease characteristics, and PB markers. PANTHER classification was used for pathway analysis. Results Genomic subtyping of high- and low-inflammation rheumatoid synovial tissues based on gene expression profiles exactly matched immunohistochemical classification. The patients with the high-inflammation tissue type had higher Disease Activity Scores in 28 joints, higher C-reactive protein levels, higher erythrocyte sedimentation rates, increased numbers of platelets, and shorter disease durations. Comparative analysis of PB gene expression profiles yielded no statistically significant differences between the 2 tissue groups at the single-gene expression level. PANTHER pathway analysis revealed a significant association of increased protein biosynthesis with high-inflammation tissue. Conclusion High-inflammation tissue is associated with more severe disease and shorter disease duration. While pathway-level analysis revealed that coordinate differential expression of genes involved in protein synthesis in PB is associated with high-inflammation tissue types, differential tissue pathology was not reflected in the PB by differential expression of single genes. [source] Cardiovascular disease in patients with inflammatory rheumatic disease is associated with up-regulation of markers of inflammation in cardiac microvessels and cardiomyocytesARTHRITIS & RHEUMATISM, Issue 3 2010Cecilia Grundtman Objective Various inflammatory rheumatic diseases (IRDs) are associated with increased mortality due to cardiovascular disease. The aim of this study was to investigate heart biopsy specimens obtained from patients undergoing coronary artery bypass grafting and compare markers of inflammation and endothelial cell activation in the cardiac and skeletal muscle of patients with and those without IRD. Methods Paired biopsy specimens of cardiac and skeletal muscle were obtained from 22 consecutive patients with IRD and 8 patients without IRD, all of whom were undergoing coronary artery bypass grafting. The biopsy specimens were evaluated in a blinded manner by conventional microscopy and digital image analysis for cell markers (CD3, CD4, CD8, CD68, CD163, and CD31), HLA (HLA,ABC, HLA,DR, and HLA,DQ), adhesion molecules (intercellular adhesion molecule 1 and vascular cell adhesion molecule 1), and proinflammatory cytokines (interleukin-1,, interleukin-1,, and tumor necrosis factor). Results Patients with IRD had significantly higher expression of adhesion molecules, proinflammatory cytokines, and all classes of HLA on cardiomyocytes and endothelial cells but no increase on mononuclear cells in the myocardium compared with patients without IRD. Furthermore, cardiac muscle from patients with IRD displayed significantly higher local expression of inflammation and activation of cardiac microvessels compared with skeletal muscle from the same patients. Conclusion Patients with cardiovascular disease had increased expression of adhesion molecules, HLA, and proinflammatory cytokines in heart tissue, indicating local inflammation involving microvessels and cardiomyocytes that could play a role in the pathogenesis of cardiovascular disease. The more pronounced changes in patients with IRD compared with patients without IRD might contribute to the increased risk of cardiovascular disease and premature death in patients with IRD. [source] Sera from anti,Jo-1,positive patients with polymyositis and interstitial lung disease induce expression of intercellular adhesion molecule 1 in human lung endothelial cellsARTHRITIS & RHEUMATISM, Issue 8 2009Sevim Barbasso Helmers Objective To investigate whether sera or purified IgG from patients with polymyositis (PM) and patients with dermatomyositis (DM), with or without interstitial lung disease (ILD), can activate endothelial cells (ECs). Methods Patients' sera were selected based on the presence or absence of anti,Jo-1, anti-SSA, or anti,U1 small nuclear RNP autoantibodies. The presence of autoantibodies was determined by line blot assays. Cultured human microvascular ECs derived from lung tissue (HMVEC-L) were incubated with sera or purified IgG from 22 patients with PM, 7 patients with DM, and 10 healthy individuals as controls. Assessment of intercellular adhesion molecule 1 (ICAM-1) expression was conducted by immunofluorescence (n = 22) and by cell-based enzyme-linked immunosorbent assay (ELISA) (n = 20). Serum levels of soluble ICAM-1 (sICAM-1) were determined by ELISA. Results Sera from PM patients with ILD who were positive for anti,Jo-1 autoantibodies had a significantly stronger effect on the expression of ICAM-1 by HMVEC-L in comparison with sera from healthy controls and patients with other autoantibodies. Purified IgG did not induce ICAM-1 expression. Higher serum levels of sICAM-1 were found in patients with myositis compared with healthy controls. Conclusion EC activation with ICAM-1 expression could contribute to the multiorgan involvement, including the development of myositis and ILD, in patients carrying anti,Jo-1 autoantibodies. The EC-activating factors are not the autoantibodies themselves, but might be systemic factors associated with these autoantibodies. [source] Induction of CCR2-dependent macrophage accumulation by oxidized phospholipids in the air-pouch model of inflammationARTHRITIS & RHEUMATISM, Issue 5 2009Alexandra Kadl Objective Macrophages are key players in the pathogenesis of rheumatoid synovitis as well as in atherosclerosis. To determine whether atherogenic oxidized phospholipids potentially contribute to synovial inflammation and subsequent monocyte/macrophage recruitment, we examined the effects of oxidized 1- palmitoyl-2-arachidonoyl- sn -3-glycero-phosphorylcholine (OxPAPC) on chemokine expression and leukocyte recruitment in a facsimile synovium in vivo using the murine air-pouch model. Methods Air pouches were raised by 2 injections of sterile air, and inflammation was induced by injecting either lipopolysaccharide (LPS) or OxPAPC into the pouch lumen. Inflammation was assessed by analysis of inflammatory gene expression using reverse transcription,polymerase chain reaction or immunohistochemical analysis, and leukocytes were quantified in the lavage fluid and in the pouch wall after staining with Giemsa or after enzymatic digestion followed by fluorescence-activated cell sorter analysis. Results Application of OxPAPC resulted in selective recruitment of monocyte/macrophages into the air-pouch wall, but not in the lumen. In contrast, LPS induced both monocyte and neutrophil accumulation in the pouch lumen as well as in the wall. LPS, but not OxPAPC, induced the expression of adhesion molecules E-selectin, P-selectin, intercellular adhesion molecule 1, and vascular cell adhesion molecule 1. OxPAPC increased the expression of the CCR2 ligands monocyte chemotactic protein 1 (MCP-1), MCP-3, and MCP-5, as well as RANTES and growth-related oncogene , (GRO,), while it down-regulated the expression of CCR2 on macrophages. Moreover, oxidized phospholipid,induced macrophage accumulation was abrogated in CCR2,/, mice. Conclusion These data demonstrate that oxidized phospholipids trigger a type of inflammatory response that leads to selective macrophage accumulation in vivo, a process relevant for the pathogenesis of chronic inflammatory rheumatic diseases. [source] Histone deacetylase 7, a potential target for the antifibrotic treatment of systemic sclerosisARTHRITIS & RHEUMATISM, Issue 5 2009Hossein Hemmatazad Objective We have recently shown a significant reduction in cytokine-induced transcription of type I collagen and fibronectin in systemic sclerosis (SSc) skin fibroblasts upon treatment with trichostatin A (TSA). Moreover, in a mouse model of fibrosis, TSA prevented the dermal accumulation of extracellular matrix. The purpose of this study was to analyze the silencing of histone deacetylase 7 (HDAC-7) as a possible mechanism by which TSA exerts its antifibrotic function. Methods Skin fibroblasts from patients with SSc were treated with TSA and/or transforming growth factor ,. Expression of HDACs 1,11, extracellular matrix proteins, connective tissue growth factor (CTGF), and intercellular adhesion molecule 1 (ICAM-1) was analyzed by real-time polymerase chain reaction, Western blotting, and the Sircol collagen assay. HDAC-7 was silenced using small interfering RNA. Results SSc fibroblasts did not show a specific pattern of expression of HDACs. TSA significantly inhibited the expression of HDAC-7, whereas HDAC-3 was up-regulated. Silencing of HDAC-7 decreased the constitutive and cytokine-induced production of type I and type III collagen, but not fibronectin, as TSA had done. Most interestingly, TSA induced the expression of CTGF and ICAM-1, while silencing of HDAC-7 had no effect on their expression. Conclusion Silencing of HDAC-7 appears to be not only as effective as TSA, but also a more specific target for the treatment of SSc, because it does not up-regulate the expression of profibrotic molecules such as ICAM-1 and CTGF. This observation may lead to the development of more specific and less toxic targeted therapies for SSc. [source] Light up-regulated on B lymphocytes and monocytes in rheumatoid arthritis mediates cellular adhesion and metalloproteinase production by synoviocytesARTHRITIS & RHEUMATISM, Issue 4 2007Young Mo Kang Objective To study the expression of LIGHT (tumor necrosis factor superfamily 14) and herpesvirus entry mediator (HVEM; tumor necrosis factor receptor superfamily 14) in rheumatoid arthritis (RA) and to determine the regulatory role of LIGHT on the effector functions of fibroblast-like synoviocytes (FLS). Methods The expression of LIGHT and HVEM was assessed by immunohistochemical staining of synovial tissue and by flow cytometric analysis of mononuclear cells. The presence of HVEM and lymphotoxin , receptor was measured by reverse transcriptase,polymerase chain reaction and by flow cytometry. The regulation of effector molecules, including matrix metalloproteinases (MMPs) and adhesion molecules, was evaluated. The adhesiveness of FLS was determined by adhesion assay. Results HVEM was detected in most cell types within rheumatoid synovial tissue, while only a few cells were positive for LIGHT. In RA patients, LIGHT expression was significantly up-regulated only in CD20+ B cells and monocytes, whereas the mean fluorescence intensity of HVEM was down-regulated in mononuclear cells. The stimulation of FLS with LIGHT resulted in the production of MMPs and the expression of adhesion molecules, which were efficiently inhibited by dexamethasone. LIGHT-mediated up-regulation of MMPs and intercellular adhesion molecule 1 was blocked by inhibitors of NF-,B and JNK, whereas up-regulation of vascular cell adhesion molecule 1 was blocked by inhibitors of phosphatidylinositol 3-kinase, as well as NF-,B. Conclusion These data suggest that binding of LIGHT with its receptors may play a role in the progression of inflammation within rheumatoid synovium, especially by mediating the interactions between infiltrating inflammatory cells and stromal cells. These findings thus emphasize the relevance of LIGHT as a potential therapeutic target in RA. [source] Increased asymmetric dimethylarginine and endothelin 1 levels in secondary Raynaud's phenomenon: Implications for vascular dysfunction and progression of diseaseARTHRITIS & RHEUMATISM, Issue 7 2003Sanjay Rajagopalan Objective To compare microvascular and macrovascular functions in a cohort of patients with primary and secondary Raynaud's phenomenon (RP) who were matched for demographic, risk factor, and severity profiles. Methods Forty patients with primary or secondary RP matched for vascular risk factors and severity scores underwent testing of endothelial function and cold pressor responsiveness of the brachial artery. Microvascular perfusion of the digital vasculature was assessed using laser Doppler fluxmetry in response to reactive hyperemia. Plasma was assayed for endothelin 1 (ET-1), asymmetric dimethylarginine (ADMA), intercellular adhesion molecule 1, vascular cell adhesion molecule 1 (VCAM-1), and monocyte chemoattractant protein 1 (MCP-1). Results Patients with RP had abnormal vasoconstrictor responses to cold pressor tests (CPT) that were similar in primary and secondary RP. There were no differences in median flow-mediated and nitroglycerin-mediated dilation or CPT of the brachial artery in the 2 populations. Patients with secondary RP were characterized by abnormalities in microvascular responses to reactive hyperemia, with a reduction in area under the curve adjusted for baseline perfusion, but not in time to peak response or peak perfusion ratio. Plasma ET-1, ADMA, VCAM-1, and MCP-1 levels were significantly elevated in secondary RP compared with primary RP. There was a significant negative correlation between ET-1 and ADMA values and measures of microvascular perfusion but not macrovascular endothelial function. Conclusion Secondary RP is characterized by elevations in plasma ET-1 and ADMA levels that may contribute to alterations in cutaneous microvascular function. [source] Association of interleukin-18 expression with enhanced levels of both interleukin-1, and tumor necrosis factor , in knee synovial tissue of patients with rheumatoid arthritisARTHRITIS & RHEUMATISM, Issue 2 2003Leo A. B. Joosten Objective To examine the expression patterns of interkeukin-18 (IL-18) in synovial biopsy tissue of patients with rheumatoid arthritis (RA), and to determine whether expression of this primary cytokine is related to the expression of other cytokines and adhesion molecules and related to the degree of joint inflammation. Methods Biopsy specimens of knee synovial tissue either without synovitis (n = 6) or with moderate or severe synovitis (n = 11 and n = 12, respectively) were obtained from 29 patients with active RA. Paraffin-embedded, snap-frozen sections were used for immunohistochemical detection of IL-18, tumor necrosis factor , (TNF,), IL-1,, IL-12, and IL-17. Furthermore, adhesion molecules, such as intercellular adhesion molecule 1, vascular cell adhesion molecule 1, and E-selectin, and cell markers CD3, CD14, and CD68 were stained. Results IL-18 staining was detectable in 80% of the RA patients, in both the lining and sublining of the knee synovial tissue. IL-18 expression in the synovial tissue was strongly correlated with the expression of IL-1, (in the sublining r = 0.72, in the lining r = 0.71; both P < 0.0001) and TNF, (in the sublining r = 0.59, P < 0.0007, and in the lining r = 0.68, P < 0.0001). In addition, IL-18 expression in the sublining correlated with macrophage infiltration (r = 0.64, P < 0.0007) and microscopic inflammation scores (r = 0.78, P < 0.0001), and with the acute-phase reaction as measured by the erythrocyte sedimentation rate (r = 0.61, P < 0.0004). Interestingly, RA synovial tissue that coexpressed IL-18 and IL-12 demonstrated enhanced levels of the Th1-associated cytokine IL-17. Conclusion Our results show that expression of IL-18 is associated with that of IL-1, and TNF, and with local inflammation in the synovial tissue of patients with RA. In addition, synovial IL-18 expression correlates with the acute-phase response. These data indicate that IL-18 is a primary proinflammatory cytokine in RA that drives the local production of IL-1, and TNF,. [source] Crystallographic characterization of the radixin FERM domain bound to the cytoplasmic tail of the adhesion protein ICAM-2ACTA CRYSTALLOGRAPHICA SECTION D, Issue 6 2001Keisuke Hamada Radixin is a member of the ERM proteins, which cross-link plasma membranes and actin filaments. The FERM domains located at the N-terminal regions of ERM proteins are responsible for membrane association through direct interactions with the cytoplasmic domains of integral membrane proteins. Here, crystals of the complex between the radixin FERM domain and the full-length cytoplasmic tail (28-residue peptide) of intercellular adhesion molecule 2, ICAM-2, have been obtained. The crystals were found to belong to space group P3121 or P3221, with unit-cell parameters a = b = 100.44,(9), c = 99.49,(6),Å, and contain one complex in the crystallographic asymmetric unit. An intensity data set was collected to a resolution of 2.60,Å. [source] Transepithelial migration of Toxoplasma gondii involves an interaction of intercellular adhesion molecule 1 (ICAM-1) with the parasite adhesin MIC2CELLULAR MICROBIOLOGY, Issue 4 2005Antonio Barragan Summary Toxoplasma gondii crosses non-permissive biological barriers such as the intestine, the blood,brain barrier and the placenta thereby gaining access to tissues where it most commonly causes severe pathology. Herein we show that in the process of migration Toxoplasma initially concentrates around intercellular junctions and probably uses a paracellular pathway to transmigrate across biological barriers. Parasite transmigration required viable and actively motile parasites. Interestingly, the integrity of host cell barriers was not altered during parasite transmigration. As intercellular adhesion molecule 1 (ICAM-1) is upregulated on cellular barriers during Toxoplasma infection, we investigated the role of this receptor in parasite transmigration. Soluble human ICAM-1 and ICAM-1 antibodies inhibited transmigration of parasites across cellular barriers implicating this receptor in the process of transmigration. Furthermore, human ICAM-1 immunoprecipitated the mature form of the parasite adhesin MIC2 present on the parasite surface, indicating that this interaction may contribute to cellular migration. These findings reveal that Toxoplasma exploits the natural cell trafficking pathways in the host to cross cellular barriers and disseminate to deep tissues. [source] Evaluating budesonide efficacy in nasal polyposis and predicting the resistance to treatmentCLINICAL & EXPERIMENTAL ALLERGY, Issue 1 2009F. C. P. Valera Summary Background Cell resistance to glucocorticoids is a major problem in the treatment of nasal polyposis (NP). Objectives The objectives of this study were to observe the effect of budesonide on the expression of IL-1,, TNF-,, granulocyte macrophage-colony stimulating factor, intercellular adhesion molecule (ICAM)-1, basic fibroblast growth factor, eotaxin-2, glucocorticoid receptor (GR)-,, GR-,, c-Fos and p65 in nasal polyps and to correlate their expression to clinical response. Methods Biopsies from nasal polyps were obtained from 20 patients before and after treatment with topical budesonide. Clinical response to treatment was monitored by a questionnaire and nasal endoscopy. The mRNA levels of the studied genes were measured by real-time quantitative (RQ)-PCR. Results There was a significant decrease in the expression of TNF-, (P<0.05), eotaxin-2 (P<0.05) and p65 (P<0.05) in NP after treatment. Poor responders to glucocorticoids showed higher expression of IL-1, (3.74 vs. 0.14; P<0.005), ICAM-1 (1.91 vs. 0.29; P<0.05) and p65 (0.70 vs. 0.16; P<0.05) before treatment. Following treatment, IL-1, (4.18 vs. 0.42; P<0.005) and GR-, (0.95 vs. 0.28; P<0.05) mRNA expression was higher in this group. Conclusion Topical budesonide reduced the expression of TNF-,, eotaxin-2 and p65. Poor responders to topical budesonide exhibit higher levels of IL-1,, ICAM-1 and nuclear factor (NF)-,B at diagnosis and higher expression of both IL-1, and GR-, after treatment. These results emphasize the anti-inflammatory action of topical budesonide at the molecular level and its importance in the treatment of NP. Nevertheless, IL-1,, ICAM-1 and NF-,B may be associated with primary resistance to glucocorticoids in NP, whereas higher expression of GR-, in poor responders only after glucocorticoid treatment may represent a secondary drug resistance mechanism in this disease. [source] Rhinovirus infection and house dust mite exposure synergize in inducing bronchial epithelial cell interleukin-8 releaseCLINICAL & EXPERIMENTAL ALLERGY, Issue 10 2008A. Bossios Summary Background Human rhinoviruses (HRVs) and house dust mites (HDMs) are among the most common environmental factors able to induce airway inflammation in asthma. Although epidemiological studies suggest that they also synergize in inducing asthma exacerbations, there is no experimental evidence to support this, nor any information on the possible mechanisms involved. Objective To investigate their interaction on the induction of airway epithelial inflammatory responses in vitro. Methods BEAS-2B cells were exposed to activated HDM Dermatophagoides pteronyssinus major allergen I (Der p I), HRVs (HRV1b or HRV16) or both in different sequences. IL-8/CXCL8 release, intercellular adhesion molecule (ICAM)-1 surface expression and nuclear factor ,B (NF-,B) translocation were evaluated. Complementary, primary human bronchial epithelial cells (HBECs) exposed to both Der p I and RVs and IL-8, IL-6, IFN-,-induced protein (IP)-10/CXCL10, IFN-,1/IL-29, regulated upon activation normal T lymphocyte expressed and secreted (RANTES)/CCL5 release were measured. Results RV and Der p I up-regulated IL-8 release, ICAM-1 expression and NF-,B translocation in BEAS-2B cells. Simultaneous exposure to both factors, as well as when cells were initially exposed to HRV and then to Der p I, resulted in further induction of IL-8 in a synergistic manner. Synergism was not observed when cells were initially exposed to Der p I and then to HRV. This was the pattern in ICAM-1 induction although the phenomenon was not synergistic. Concurrent exposure induced an early synergistic NF-,B translocation induction, differentiating with time, partly explaining the above observation. In HBECs, both HRV and Der p I induced IL-8, IL-6, IL-29 and IP-10, while RANTES was induced only by HRV. Synergistic induction was observed only in IL-8. Conclusion HRV and enzymatically active Der p I can act synergistically in the induction of bronchial epithelial IL-8 release, when HRV infection precedes or is concurrent with Der p I exposure. Such a synergy may represent an important mechanism in virus-induced asthma exacerbations. [source] Heterogeneity in lipopolysaccharide responsiveness of endothelial cells identified by gene expression profiling: role of transcription factorsCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 3 2006G. C. Beck Summary Interindividual differences of endothelial cells in response to endotoxins might contribute to the diversity in clinical outcome among septic patients. The present study was conducted to test the hypothesis that endothelial cells (EC) with high and low proinflammatory potential exist and to dissect the molecular basis underlying this phenomenon. Thirty human umbilical vein endothelial cell (HUVEC) lines were stimulated for 24 h with lipopolysaccharide (LPS) and screened for interleukin (IL)-8 production. Based on IL-8 production five low and five high producers, tentatively called types I and II responders, respectively, were selected for genome-wide gene expression profiling. From the 74 genes that were modulated by LPS in all type II responders, 33 genes were not influenced in type I responders. Among the 41 genes that were increased in both responders, 17 were expressed significantly stronger in type II responders. Apart from IL-8, significant differences in the expression of proinflammatory related genes between types I and II responders were found for adhesion molecules [intercellular adhesion molecule (ICAM-1), E-selectin)], chemokines [monocyte chemoattractant protein (MCP-1), granulocyte chemotactic protein (GCP-2)], cytokines (IL-6) and the transcription factor CCAAT/enhancer binding protein-delta (C/EBP-,). Type I responders also displayed a low response towards tumour necrosis factor (TNF)-,. In general, maximal activation of nuclear factor (NF)-,B was achieved in type I responders at higher concentrations of LPS compared to type II responders. In the present study we demonstrate that LPS-mediated gene expression differs quantitatively and qualitatively in types I and II responders. Our results suggest a pivotal role for common transcription factors as a low inflammatory response was also observed after TNF-, stimulation. Further studies are required to elucidate the relevance of these findings in terms of clinical outcome in septic patients. [source] Cholinergic control of epidermal cohesionEXPERIMENTAL DERMATOLOGY, Issue 4 2006Sergei A. Grando Abstract:, The non-neuronal cholinergic system of human epidermis includes the keratinocyte (KC) acetylcholine (ACh) axis composed of the enzymes mediating ACh synthesis and degradation, and two classes of ACh receptors, the nicotinic and muscarinic ACh receptors, mediating biological effects of the cutaneous cytotransmitter ACh. Regulation of KC cell,cell and cell,matrix adhesion is one of the important biological functions of cutaneous ACh. The downstream targets of ACh effects mediated by distinct ACh receptor subtypes include both the intercellular adhesion molecules, such as classical and desmosomal cadherins, and integrins mediating KC adhesion to a substrate. The signaling pathways include activation or inhibition of kinase cascades resulting in either up- or down-regulation of the expression of cell adhesion molecules or changes in their phosphorylation status, or both. The components of the KC ACh axis are involved in cutaneous blistering in patients with autoimmune pemphigus, junctional and dystrophic forms of epidermolysis bullosa, thermal burns, and mustard-induced vesication. Recent progress with the development of antiacantholytic therapies of patients with pemphigus using cholinomimetics indicates that cholinergic drugs may be a promising approach for other cutaneous blistering disorders. [source] Expression of intercellular adhesion molecule (ICAM)-1 or ICAM-2 is critical in determining sensitivity of pancreatic cancer cells to cytolysis by human ,,-T cells: Implications in the design of ,,-T-cell-based immunotherapies for pancreatic cancerJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 5 2009Zhiyong Liu Abstract Background and Aims:, ,,-T cells can recognize and kill malignant cells, particularly those of epithelial origin, through mechanisms which do not require the recognition of tumor-specific antigens (innate immune response). This natural ability of ,,-T cells to kill tumor cells in a tumor antigen-independent manner provides a strong rationale for developing clinical trials designed to exploit the innate antitumor properties of ,,-T cells. Methods:,In vitro studies were carried out to asses the sensitivity of pancreatic cancer cells (MIA PaCa2, BxPC-3, PANC-1) to killing by ex vivo expanded human ,,-T cells. Results:, The capacity of ,,-T cells to bind to as well as to kill pancreatic cancer cells correlated with the degree of surface expression of key intercellular adhesion molecules (ICAM) present on pancreatic cancer cells. Moreover, pancreatic cancer cells expressing neither ICAM-1 nor ICAM-2 were bound poorly by ,,-T cells and were found to be resistant to ,,-T-cell killing. However, upon transfection of resistant cells with ICAM-1 or ICAM-2, ,,-T cells were then able to bind to and subsequently kill these cells. Conclusion:,In vitro, the expression of ICAM-1 or ICAM-2 on human pancreatic cancer cells is critically important in determining the extent to which these cells are sensitive to killing by human ,,-T cells. Accordingly, in ongoing and future clinical studies using ,,-T cells for the treatment of a variety of epithelial-derived solid tumors,including pancreatic cancer,interventions intended to modulate ICAM expression on tumor cells may become important adjuncts to ,,-T-cell-based immunotherapies. [source] Deranged expression of the E-cadherin/,-catenin complex and the epidermal growth factor receptor in the clinical evolution and progression of oral squamous cell carcinomasJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 8 2002Agnes Bánkfalvi Abstract Background:, Deranged expression and function of the E-cadherin/,-catenin (E-cad/,-cat) complex and the epidermal growth factor receptor (EGFR) have been implicated in the development and progression of carcinomas. Methods:, To estimate the role of these molecules in oral cancer, we investigated 75 primary oral squamous cell carcinomas (OSCCs) with adjacent normal and/or dysplastic mucosa, 30 paired metastases and 12 recurrences by immunohistochemistry. Results:, All three molecules were constitutionally expressed in the basal/parabasal layers of tumour adjacent ,normal' epithelium, in contrast to a significant increase of EGFR and heterogeneous expression of E-cad/,-cat in dysplasia. In OSCCs, over-expression of EGFR correlated significantly with lower tumour grade and poor prognosis, loss of E-cad was a significant marker for shortened survival, reduced ,-cat staining was a predictive marker for lymph node metastasis. Conclusions:, There is a perturbance in intercellular adhesion molecules and EGFR expression/function in oral cancer with major clinical impact. E-cad and ,-cat seem to inhibit EGFR to enhance the progression of OSCCs. [source] | |||||||||||||