Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We here report the finding that the anti-inflammatory cytokine interleukin-10 (IL-10) inhibits motility of B lymphocytes. B cells were induced to display motile morphology and active migration by IL-4. IL-10 inhibited locomotor responses to IL-4, when B cells of both murine and human origin were used. The inhibitory effect of IL-10 was reversible, since washing of B cells preincubated in IL-10 restored the ability to respond to IL-4. Time-course experiments showed that IL-10 did not have to be present from the very onset of culture, but could be added as late as 5 hr after initiation. In addition, murine B cells stimulated with lipopolysaccharide (LPS) showed motile morphology, as well as cellular aggregation and proliferation. All these parameters were suppressed by IL-10. However, viability of B cells was not adversely affected by IL-10. Exposure to IL-10 did not result in any changes in the surface expression of molecules involved in adhesion, such as CD2, CD11a/CD18, CD44, CD54 or L-selectin, on B lymphocytes.
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PMID:Interleukin-10 inhibits motility in murine and human B lymphocytes. 795 71

To investigate the role of polymorphonuclear leukocytes in galactosamine-induced hepatic injury, we injected rats intraperitoneally with antiserum against rat polymorphonuclear leukocytes to deplete circulating neutrophils, then administered galactosamine plus lipopolysaccharide. Polymorphonuclear leukocytes in the hepatic sinusoids were increased after administration of galactosamine plus lipopolysaccharide, whereas pretreatment with the antiserum decreased the number of circulating leukocytes and reduced the mortality and the severity of hepatic injury. Serum collected 1 hr after galactosamine/lipopolysaccharide treatment enhanced in vitro polymorphonuclear leukocyte adherence to hepatic endothelial cells and induced leukocyte superoxide production. Intercellular adhesion molecule-1 expression on hepatic endothelial cells was also enhanced after stimulation with the serum. Polymorphonuclear leukocyte adhesion was partially inhibited by an antibody against tumor necrosis factor-alpha but not by superoxide dismutase. These results suggest that polymorphonuclear leukocytes play an important role in galactosamine-induced hepatic injury and that the accumulation and activation of leukocytes, as well as the enhanced expression of adhesion molecules on hepatic endothelial cells, can be induced by biologically active mediators such as tumor necrosis factor-alpha. In addition, prostaglandins E1 and E2 lessened the enhanced adherence of polymorphonuclear leukocytes and thus contributed to protection against hepatic injury.
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PMID:Role of polymorphonuclear leukocytes in galactosamine hepatitis: mechanism of adherence to hepatic endothelial cells. 798 55

Cell adhesion molecules are surface proteins important for cell migration and adhesion and are strongly expressed in eyes with inflammation. We studied the expression of two cell adhesion molecules: intercellular adhesion molecule-1 (ICAM-1, CD54) and lymphocyte function-associated antigen-1 (LFA-1, CD11a/CD18) in mice with experimental autoimmune uveitis. B10.A mice were immunized with interphotoreceptor retinoid-binding protein and eyes were serially examined for expression of cell adhesion molecules using immunohistochemical staining. ICAM-1 was expressed on the vascular endothelium of the ciliary body and retina by 7 days after immunization, and LFA-1 was first expressed on some infiltrating inflammatory cells 9 days after immunization. Clear histologic evidence of ocular inflammation did not occur until 11 days after immunization. We then studied the effect of monoclonal antibodies against ICAM-1 and LFA-1 on the development of experimental autoimmune uveitis. Three groups of mice were immunized and treated for 21 days with daily intraperitoneal injections of rat monoclonal antibody against murine ICAM-1 or LFA-1 or with rat IgG as control. Ocular inflammation, graded clinically by examination of the fundus 14 and 21 days after immunization, was significantly decreased in animals treated with anti-ICAM-1 (P < 0.01 at Days 14 and 21) and with anti-LFA-1 antibody (P < 0.01 at Days 14 and 21). The intraocular inflammation graded histologically was also decreased in mice treated with anti-ICAM-1 and anti-LFA-1 antibody. This difference in the histologic grade of inflammation was statistically significant (P < 0.02) between mice treated with anti-ICAM-1 antibody and control mice and approached statistical significance (P < 0.10) in mice treated with anti-LFA-1 antibody compared to the control mice. Proliferative responses to lipopolysaccharide, PPD, and interphotoreceptor binding protein of lymphocytes obtained from the draining lymph nodes of mice treated with the antibodies were lower than those from the control mice, suggesting that cell-cell binding was impaired in treated mice. These data show that ICAM-1 is expressed in the eye before histologic evidence of inflammation, and that monoclonal antibodies against ICAM-1 and LFA-1 are effective in inhibiting experimental autoimmune uveitis in mice.
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PMID:Monoclonal antibodies against ICAM-1 (CD54) and LFA-1 (CD11a/CD18) inhibit experimental autoimmune uveitis. 810 Jan 90

Intercellular adhesion molecule-1 (ICAM-1, CD54) is a cell-surface glycoprotein which has been shown to play an important role for cell/cell interaction. Little is known about its occurrence in the murine monocyte/macrophage (M phi) lineage; hence, we analyzed ICAM-1 expression in cells and cell lines representing different stages of M phi maturation and studied its regulation during inflammatory activation. Flow cytometric analysis of bone marrow-derived M phi cultured in the presence of M-CSF, of thioglycollate-elicited peritoneal M phi and of M1 myeloblasts differentiated by lipopolysaccharide (LPS) treatment revealed that ICAM-1 is increasingly expressed during monocytic maturation. Accordingly, the myelomonocytic cell lines RMB.TG, WEHI.TG, J774A and P388D, which can be ordered in a linear differentiation sequence, showed increasing levels of ICAM-1 expression. Furthermore, ICAM-1 expression by bone marrow-derived M phi could be up-regulated by tumor necrosis factor-alpha, interferon-gamma and LPS. In two models of murine experimental inflammation, i.e. induction phase of contact hypersensitivity and cutaneous leishmaniasis, which are both dependent on M phi/T cell interaction, M phi expressing ICAM-1 were found to be highly abundant. In addition, it was demonstrated that co-culture of Leishmania maior parasites with bone marrow M phi led to up-regulation of ICAM-1 on these cells. In conclusion, our data clearly demonstrate that ICAM-1 is increasingly being expressed during maturation of murine M phi. Cytokines and inflammatory stimuli modulate M phi ICAM-1 expression as well thus referring to its considerable role during inflammation, e.g. providing accessory or costimulatory signals for T cell activation.
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PMID:Expression of intercellular adhesion molecule-1 by murine macrophages is up-regulated during differentiation and inflammatory activation. 810 78

The role of platelets was investigated in two models of lipopolysaccharide (LPS)-induced toxicity in mice: the systemic reaction, provoked by intravenous LPS injection in D-galactosamine-sensitized recipients, which results in host death, and the local reaction, elicited in the skin by sequential injections of LPS and tumor necrosis factor alpha at 24-h intervals, which results in hemorrhagic necrosis. In both models, the depletion of platelets with a rabbit polyclonal or a mouse monoclonal antiplatelet immunoglobulin G afforded significant protection. In the local reaction, studies of the distribution of 111In-labelled platelets as well as optical and electron microscopy showed that platelets are localized in the dermal venules before hemorrhage occurs. Anti-CD11a (LFA-1) and anti-CD54 (ICAM-1) monoclonal antibodies prevented both platelet localization and hemorrhagic necrosis, and these determinants were detected on mouse platelets by immunofluorescence. The antiplatelet monoclonal antibody did not reduce the localization of polymorphonuclear leukocytes in the dermal venules, as shown by histological sections. Thus, in the local reaction, the stimulation with LPS and tumor necrosis factor alpha leads to a binding of platelets to the endothelium of venules by their beta 2 integrins, which seems necessary for the development of the hemorrhagic necrosis.
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PMID:An effector role for platelets in systemic and local lipopolysaccharide-induced toxicity in mice, mediated by a CD11a- and CD54-dependent interaction with endothelium. 810 95

Sialic acids decorating blood and cell surface proteins can play important roles in various biological processes. The inflammatory cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin-1, as well as bacterial lipopolysaccharide, can activate vascular endothelium, increasing expression of several surface glycoproteins. Here we show that treatment of cultured human endothelial cells (HEC) with TNF-alpha, interleukin-1, or lipopolysaccharide causes increased expression of the enzyme beta-galactoside alpha-2,6-sialytransferase (alpha 2-6STN). TNF-alpha was most effective, inducing a 3.5-fold enhancement of cell-associated sialytransferase activity by 72 h. In addition, activated HEC secreted a large portion of the induced sialyltransferase activity into the medium. Analysis of labeled HEC showed both a relative and an absolute increase of alpha 2,6-linked sialic acid on N-linked oligosaccharides after TNF-alpha stimulation. This coincided with increased expression of endothelial glycoproteins bearing N-linked glycans with alpha 2,6-linked sialic acid detected by the lectin Sambucus nigra agglutinin. The cytokine-inducible endothelial cell adhesion molecules E-selectin, ICAM-1, and VCAM-1 are among these glycoprotein substrates for alpha 2-6STN. These changes also correlated with a substantial increase in binding sites for CD22 beta, a mammalian lectin known to recognize oligosaccharides carrying multiple copies of alpha 2,6-linked sialic acid. Northern analysis revealed increased levels of mRNA encoding alpha 2-6STN. Thus, activation of endothelial cells during inflammatory and immunological processes may induce alpha 2-6STN, which can participate in sialylation of other activation-dependent molecules.
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PMID:Cytokine-induced beta-galactoside alpha-2,6-sialyltransferase in human endothelial cells mediates alpha 2,6-sialylation of adhesion molecules and CD22 ligands. 814 53

WEHI-231 is a murine lymphoma generally considered to represent an immature B cell. Cross-linking of slg on WEHI-231 leads to growth arrest and eventually physiological cell death (PCD). We characterized three sublines of WEHI-231 by flow cytometry and compared their responses with slg cross-linking. All sublines had identical expression of a series of common B cell surface markers (IgM, IgD, Fc gamma R, ICAM-1, and CD45), but one was I-A-. Despite the phenotypic similarities between these sublines, anti-IgM caused aptotosis in only two sublines, although it inhibited growth in all three. The growth arrest induced by anti-IgM was reversible by lipopolysaccharide and Th2 clones and independent of Fc gamma R engagement. Anti-IgD, unlike anti-IgM, induced neither growth arrest nor apoptosis. To further compare the sublines' susceptibility to PCD, we investigated their responses to anti-IgM by ultrastructural morphology, [3H]thymidine release, propidium iodide exclusion, and incorporation into DNA. By all these experimental criteria, two of the WEHI-231 sublines were susceptible to PCD while the third demonstrated remarkable resistance to anti-IgM, but not irradiation or Th1-induced PCD. This differential susceptibility to PCD did not correlate with either bcl-2 levels in the resting cells or to the decrease in bcl-2 expression following slg engagement. We discuss the implications of these findings for our understanding of PCD in B cells.
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PMID:Physiological cell death in B lymphocytes: I. Differential susceptibility of WEHI-231 sublines to anti-Ig induced physiological cell death and lack of correlation with bcl-2 expression. 814 21

Endothelial cells (EC) are very responsive to proinflammatory cytokines, e.g. interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF alpha), as well as to bacterial lipopolysaccharide. EC are stimulated by these substances to secrete chemotactic factors and to increase expression of cell adhesion molecules (CAM), leading to dramatically altered interactions with leukocytes, e.g. granulocytes and monocytes. In these interactions E-selectin, ICAM-1 and VCAM-1 are known to play an important role, as they are presented by the EC and interact with corresponding ligands on the white blood cell membranes. These adhesion molecules have been studied worldwide in a variety of in vitro experiments using cultured EC. Different passages and mixtures of passages have been used in these experiments, often without any regard to the comparability of the results. In this study the expression of E-selectin, ICAM-1 and VCAM-1 on cultured human umbilical vein EC (HUVEC) obtained from different passages (passages 1-6) was studied after 4, 8 and 24 h of exposure to IL-1 beta and TNF alpha. In previous studies, we have shown that IL-1 beta and TNF alpha increase the expression of E-selectin and ICAM-1 on the cytoplasmatic membranes of HUVEC and human adult EC from the saphenous vein and femoral artery in a similar fashion. Using a comparative quantitative cell enzyme immunoassay, we found that the expression of the adhesion molecules was significantly reduced with increasing passages. There was also a decreased persistence of CAM comparing different periods of stimulation between 6 and 24 h in the different passages. These data indicate that the number of passages plays an important role in the expression of adhesion molecules on EC. The results are relevant for the meaningful planning of comparative in vitro studies on EC presentation of CAM.
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PMID:Comparative studies on vascular endothelium in vitro. 3. Effects of cytokines on the expression of E-selectin, ICAM-1 and VCAM-1 by cultured human endothelial cells obtained from different passages. 855 4

Inflammation is characterized by the migration of polymorphonuclear leukocytes from the vasculature into the tissue causing profound injury. Adhesion and migration of neutrophils across the vascular bed are governed by a series of complex events including cytokine/chemokine production which in turn orchestrates the temporal expression of a cohort of adhesion molecules mediating the migration. Many of these adhesion molecules and their inducers are under the control of inflammatory response transcriptional factors such as NF kappa B and AP-1. Recently we showed tepoxalin, previously known as a dual cyclooxygenase/lipoxygenase (CO/LO) inhibitor, to be a potent inhibitor of NF kappa B-induced transcription in vitro. In this study, we demonstrated that when administered in vivo, tepoxalin but not naproxen (a nonsteroidal anti-inflammatory drug, NSAID) or zileuton (an LO inhibitor), effectively inhibits neutrophil migration into inflammatory sites in murine skin stimulated by either lipopolysaccharide (LPS) or tumor necrosis factor-alpha. Immunohistochemical analysis indicates that 10-50 mg/kg of tepoxalin inhibits neutrophil migration. It also effectively blocks the upregulation of Mac-1 (CD11b/CD18) on neutrophils. Quantitative polymerase chain reaction Mac-1 analysis shows that LPS-induced transcription of E-selectin mRNA was dramatically suppressed by both 25 and 50 mg/kg of tepoxalin, whereas the level of ICAM-1 was only affected by 50 mg/kg of tepoxalin. Since it has been documented that the expression of E-selectin and Mac-1 is regulated either directly or indirectly by the transcription factor NF kappa B, our studies provide in vivo evidence that tepoxalin is a potent inhibitor of NF kappa B-mediated events in animal models and this novel molecular mechanism clearly defines it as a new class of anti-inflammatory compounds.
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PMID:Tepoxalin blocks neutrophil migration into cutaneous inflammatory sites by inhibiting Mac-1 and E-selectin expression. 856 54

Tumor necrosis factor (TNF) has a pivotal role in the pathogenesis of sepsis and septic shock. Suppression of its biosynthesis might therefore be one of the strategies in the treatment of sepsis. When peripheral white blood cells were stimulated with either E. coli lipopolysaccharide (LPS) or Staphylococcus aureus, pentoxifiline (PTX) inhibited TNF production. In contrast, only a moderate inhibitory effect was observed on the induction of interleukin 6 (IL-6). PTX inhibited not only the TNF production of monocytes, but also the TNF secretion of both granulocytes and unseparated whole blood. The in vitro TNF and IL-6 producing capacities were higher in septic patients (n = 31) than in healthy blood donors (n = 15). Administration of PTX (400 mg/day) to 20 of the septic patients resulted in TNF production similar to that found in healthy controls. It also subsequently led to an improvement of the clinical status classified by the APACHE II score. The soluble intercellular adhesion molecule-1 (sICAM-1) level was significantly higher in the sera of septic patients before PTX treatment (800-1200 ng/ml) than in normal individuals (50-150 ng/ml), but it decreased following PTX therapy. Cytofluorometric analysis revealed that the expression of ICAM-1 on stimulated mononuclear cells was inhibited by PTX. It is presumed that the suppressive effect of pentoxifylline on TNF production may be of clinical importance, improving the therapeutic strategies in septic syndrome.
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PMID:Inhibition of tumor necrosis factor production and ICAM-1 expression by pentoxifylline: beneficial effects in sepsis syndrome. 857 38


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