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Adhesion Molecules ICAM-1 (adhesion + molecule_icam-1)
Selected AbstractsSynthetic double-stranded RNA induces multiple genes related to inflammation through Toll-like receptor 3 depending on NF-,B and/or IRF-3 in airway epithelial cellsCLINICAL & EXPERIMENTAL ALLERGY, Issue 8 2006S. Matsukura Summary Background We hypothesized that synthetic double-stranded (ds)RNA may mimic viral infection and induce expression of genes related to inflammation in airway epithelial cells. Objective We analysed what gene was up-regulated by synthetic dsRNA poly I : C and then focused this study on the role of Toll-like receptor 3 (TLR3), a receptor of dsRNA and its transcriptional pathway. Methods Airway epithelial cell BEAS-2B and normal human bronchial epithelial cells were cultured in vitro. Expression of targets RNA and protein were analysed by PCR and ELISA. Localization of TLR3 expression in the cells was analysed with flow cytometry. To analyse the role of TLR3 and transcription factors, knockdown of these genes was performed with short interfering RNA (siRNA). Results Real-time PCR revealed that poly I : C significantly increased the expression of mRNAs for chemokines IP-10, RANTES, LARC, MIP-1,, IL-8, GRO-, and ENA-78 and cytokines IL-1,, GM-CSF, IL-6 and the cell adhesion molecule ICAM-1 in both cell types. Increases in protein levels were also observed. Expression of these genes was significantly inhibited in BEAS-2B cells in which TLR3 expression was knocked down. However, pre-treatment with anti-TLR3 mAb, which interferes with the function of TLR3 expressed on the cell surface, did not inhibit the genes expression and these data were concordant with the results that TLR3 was expressed inside airway epithelial cells. The study of siRNA for NF-,B and IRF3 showed that they transduce the signal of poly I : C, but their roles were different in each target gene. Conclusion TLR3 is expressed inside airway epithelial cells and transduces synthetic dsRNA signals. These signals may increase expression of inflammatory cytokines, chemokines and ICAM-1 through activation of transcription factors NF-,B and/or IRF3 in airway epithelial cells. [source] Microcirculatory Dysfunction in Chronic Venous Insufficiency (CVI)MICROCIRCULATION, Issue S1 2000MICHAEL JÜNGER ABSTRACT The elevated ambulatory pressure in the peripheral venous system of chronic venous insufficiency (CVI) patients manifests itself not only in the form of disturbed macrocirculation but also and particularly in microangiopathic changes. For this reason, it is closely correlated with trophic disorders of the skin and can ultimately lead to ulceration. Using microcirculation research techniques, we are able to provide clear evidence of a typical microangiopathy in chronic venous insufficiency. Fifty CVI patients in Widmer stages I, II, and III were examined with fluorescence video microscopy, intravital video capillaroscopy, transcutaneous oxygen partial pressure measurement, TcpO2 and laser Doppler flowmetry. The effects of compression therapy with individually fitted compression stockings on capillary morphology were studied over a period of 4 weeks in 20 CVI patients in Widmer stages I and II. The capillary pressure was measured during simulated muscle contraction using a servo-null micropressure system. We periodically drew blood from the dorsalis pedis vein and a brachial vein of 11 healthy test persons and 8 patients with stage III CVI during experimental venous hypertension in order to evaluate the expression pattern of leukocyte adhesion molecules involved in inflammation: LFA-1 (CD11a), Mac-1 (CD11b), p150,95 (CD11c), CD18, VLA-4 (CD49d), and L-selectin (CD62L). In the same patients, we used immunohistochemical methods to examine clinically unaffected skin and the skin near an ulcer, focusing on the adhesion molecules ICAM-1, VCAM-1, and E-selectin. The microangiopathic changes observed with worsening clinical symptoms include a decrease in the number of capillaries, glomerulus-like changes in capillary morphology, a drop in the oxygen content (tcpO2) of the skin, increased permeability of the capillaries to low-molecular-weight substances, increased laser Doppler flux reflecting elevated subcutaneous flow, and diminished vascular reserve. These microangiopathic changes worsen in linear proportion to the clinical severity of chronic venous insufficiency. In patients with venous ulcerations, the baseline expression of LFA-1 and VLA-4 on lymphocytes, Mac-1 expression on the myeloid cell line, and L-selectin expression on all three cell lines was not significantly different from that in healthy controls. During orthostatic stress, there was a significant reduction in the expression of L-selectin in blood cells collected at foot level in the controls (p = 0.002), but not in the patients. Clinical improvement by compression therapy was accompanied by an increase in the number of nutritive capillaries, while the diameter of the capillaries and the dermal papillae was reduced. When ulcers healed in a short period (<6 weeks), we observed a concomitant increase in the number of capillaries (p < 0.05). Microangiopathy appears before trophic disorders of the skin develop. Even trophically normal skin areas may have dilated nutritive capillaries, an early sign of disturbed skin perfusion. These changes represent a plausible explanation for the development and to recurrency tendency of venous ulcers. The reduced expression of lymphocytic L-selectin in healthy controls during the orthostatic stress test may be an indication that the cells are activated by venous stasis. Clinically effective therapeutic measures improve the impaired microcirculation of the skin in the ankle area. [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] Post-transplant reactivation of hepatitis C virus: lymphocyte infiltration and the expression of adhesion molecules and their ligands in liver allografts,APMIS, Issue 4 2006KATRI LIPSON Hepatitis C virus (HCV) recurrence after liver transplantation has been associated with chronic rejection. Biopsies from 10 patients with post-transplant HCV were examined for expression of adhesion molecules ICAM-1, VCAM-1, and ELAM-1, number of lymphocytes positive for their ligands LFA-1, VLA-4, and SLeX, and activation markers MHC class II antigens and IL2-R by immunohistochemistry. The phenotypes of the graft-infiltrating lymphocytes were determined. Results were compared to those for patients with normal graft function or rejection. Five recipients with HCV reactivation and one with de novo HCV had a biopsy available showing induction of ICAM-1 in sinusoidal endothelium (p<0.05) and hepatocytes (p<0.01), and Class II antigens in hepatocytes (p<0.01), compared to normal controls. Lymphocytes in the graft infiltrate expressed LFA-1, VLA-4, and Class II antigens, but IL2-R was not significantly expressed. CD3+, CD4+, and CD8+ cells were observed. In our study, HCV recurrence was not associated with acute or chronic rejection, and the inflammation was due to the viral infection. [source] Inhibition of glycogen synthase kinase-3, attenuates the development of carrageenan-induced lung injury in miceBRITISH JOURNAL OF PHARMACOLOGY, Issue 6 2006S Cuzzocrea Background and purpose: Glycogen synthase kinase-3 (GSK-3) is a ubiquitous serine-threonine protein kinase that participates in a multitude of cellular processes and has recently been implicated in the pathophysiology of a number of diseases. The aim of this study was to investigate the effects of GSK-3, inhibition in a model of acute inflammation. Here, we have investigated the effects of TDZD-8, a potent and selective GSK-3, inhibitor, in a mouse model of carrageenan-induced pleurisy. Experimental approach: Injection of carrageenan into the pleural cavity of mice elicited an acute inflammatory response characterized by: accumulation of fluid containing a large number of neutrophils (PMNs) in the pleural cavity, infiltration of PMNs in lung tissues and subsequent lipid peroxidation, and increased production of nitrite/nitrate (NOx), prostaglandin E2 (PGE2), tumour necrosis factor-,, (TNF-,) and interleukin-1, (IL-1,). Furthermore, carrageenan induced an upregulation of the adhesion molecules ICAM-1 and P-selectin, iNOS, COX-2 as well as nitrotyrosine as determined by immunohistochemical analysis of lung tissues. Key results: Administration of TDZD-8 (1, 3 or 10 mg kg,1, i.p.), 30 min prior to injection of carrageenan, caused a dose-dependent reduction in all the parameters of inflammation measured. Conclusions and Implications: Thus, based on these findings we propose that inhibitors of the activity of GSK-3,, such as TDZD-8, may be useful in the treatment of various inflammatory diseases. British Journal of Pharmacology (2006) 149, 687,702. doi:10.1038/sj.bjp.0706902 [source] Inhibition of LPS-induced chemokine production in human lung endothelial cells by lipid conjugates anchored to the membraneBRITISH JOURNAL OF PHARMACOLOGY, Issue 7 2002G Ch Beck In acute respiratory distress syndrome (ARDS) induced by endotoxins, a high production of inflammatory mediators by microvascular lung endothelial cells (LMVEC) can be observed. Activation of cells by endotoxins may result in elevated secretion of phospholipase A2 (sPLA2) which is thought to contribute to tissue damage. The present study was undertaken to investigate the role of sPLA2 in chemokine production in human lung microvascular endothelial cells (LMVEC) stimulated with the endotoxins lipopolysaccharide (LPS) and lipoteichoic acid (LTA). In particular, we investigated the effects of sPLA2 inhibitors, specifically, the extracellular PLA2 inhibitors (ExPLIs), composed of N-derivatized phosphatidyl-ethanolamine linked to polymeric carriers, and LY311727, a specific inhibitor of non-pancreatic sPLA2. ExPLIs markedly inhibited LPS and LTA induced production and mRNA expression of the neutrophile attracting chemokines IL-8, Gro-, and ENA-78, as well as of the adhesion molecules ICAM-1 and E-selectin. Concomitantly, ExPLIs inhibited the LPS-induced activation of NF-,B by LPS but not its activation by TNF-, or IL-1. Endotoxin mediated chemokine production in LMVEC seems not to involve PLA2 activity, since LPS stimulation was not associated with activation of intracellular or secreted PLA2. It therefore seems that the inhibitory effect of the ExPLIs was not due to their PLA2 inhibiting capacity. This was supported by the finding that the LPS-induced chemokine production was not affected by the selective sPLA2 inhibitor LY311727. It is proposed that the ExPLIs may be considered a prototype of potent suppressors of specific endotoxin-induced inflammatory responses, with potential implications for the therapy of subsequent severe inflammation. British Journal of Pharmacology (2002) 135, 1665,1674; doi:10.1038/sj.bjp.0704618 [source] | ||||||||||