UNIPROT:P43026 - FACTA Search

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Query: UNIPROT:P43026 (lipopolysaccharide)
62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The role of mucosal fibroblasts in intestinal inflammatory reactions is not known. In this study, we demonstrate that fibroblasts grown from histologically normal human duodenal biopsy tissues expressed mRNA genes for granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-1 alpha, IL-1 beta, IL-6, IL-8, IL-10, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) when stimulated with lipopolysaccharide (LPS) or IL-1 alpha. The increased mRNA expression of GM-CSF, IL-1 alpha, IL-1 beta, IL-6 and IL-8 in response to IL-1 alpha and LPS stimulation was time- and dose-dependent. In contrast, IL-10 was weakly expressed when fibroblasts were stimulated with LPS, IL-1 alpha or tumour necrosis factor-alpha (TNF-alpha), but the expression was enhanced in the presence of cycloheximide combined with optimal concentrations of LPS, IL-1 alpha or TNF-alpha, IL-1 alpha was a more potent stimulator than LPS for GM-CSF, IL-6, IL-8 and IL-10 expression, but not for IL-1 alpha and IL-1 beta. Increased GM-CSF, IL-6 and IL-8 gene expression was associated with the production of cytokine proteins in culture supernatant, but IL-1 alpha and IL-1 beta remained undetectable. Dexamethasone suppressed both gene expression and protein production of GM-CSF, IL-6 and IL-8 when fibroblasts were exposed to IL-1 alpha. TNF-alpha stimulated the release of GM-CSF, IL-6 and IL-8 and, combined with IL-1 alpha, cytokine production was enhanced synergistically. Finally, both LPS and IL-1 alpha up-regulated ICAM-1 and VCAM-1 gene expression. These findings implicate duodenal fibroblasts in the initiation and/or regulation of intestinal inflammation.
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PMID:GM-CSF, IL-1 alpha, IL-1 beta, IL-6, IL-8, IL-10, ICAM-1 and VCAM-1 gene expression and cytokine production in human duodenal fibroblasts stimulated with lipopolysaccharide, IL-1 alpha and TNF-alpha. 800 13

Vascular congestion and liver swelling have long been recognized as features of the hepatotoxic effects of acetaminophen (AAP) in mice and rats and have been proposed as contributing factors to the eventual extent of necrosis produced. Neutrophil accumulation in the hepatic microcirculation has been proposed as being responsible for the blockage of hepatic blood flow and thereby the expansion of the region of damage. We therefore determined in mice the effects of hepatotoxic doses of AAP on the messenger RNA for intercellular adhesion molecule-1 (ICAM-1), which is a critical determinant of neutrophil adhesion, activation and ultimately of neutrophil-mediated tissue injury. Hepatotoxic doses of AAP did not upregulate ICAM-1 messenger RNA. However, doses of bacterial lipopolysaccharide (LPS) did cause a rapid and dramatic increase in ICAM-1 message, which was accompanied by a much greater hepatic accumulation of neutrophils, but which led to only scattered single cell necrosis. In addition, we investigated the effects of pentoxifylline (PTX) on AAP-induced vascular congestion and on hepatic necrosis as evaluated histologically and by measurement of plasma transaminase activities. Although PTX has been shown to increase blood cell deformability and improve vascular perfusion in a number of animal models of restricted blood flow, and is used in humans for the treatment of intermittent claudication, we found no decrease in AAP-induced hepatic swelling or in AAP-induced necrosis in response to PTX. With some dosing regimens, PTX-treated animals proved to be slightly more susceptible to AAP, which may be related to the reported potentiation of the cytotoxicities of a number of alkylating anti-cancer drugs by PTX and other methylxanthines. We conclude from these studies that upregulation of ICAM-1 and subsequent adhesion and vascular plugging by neutrophils are not significant determinants of AAP-induced liver swelling and necrosis and that whatever hemorheological advantages PTX might offer in AAP-induced hepatic damage appear to be overshadowed by effects that potentiate the toxic responses.
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PMID:Investigation of possible mechanisms of hepatic swelling and necrosis caused by acetaminophen in mice. 809 17

Exposure (24 hr) to a single intratracheal administration of gallium arsenide (GaAs; 200 mg/kg) has been shown to suppress antibody production as well as other T cell-mediated immunological functions. GaAs has also been shown to exert toxic effects on events occurring early in the antibody-forming cell response which may include lymphocyte activation and proliferation. Studies were undertaken to determine whether GaAs exposure resulted in the inability of T and B lymphocytes to proliferate in response to an antigenic stimulus. During the first 24 hr after in vitro immunization with sheep red blood cells, GaAs-exposed splenocytes were suppressed 51% in their ability to proliferate compared to the vehicle (0.05% Tween 80 in saline; VH) control. There was no significant difference in absolute numbers of cluster designation (CD)8+ cells between VH- and GaAs-exposed cultures. There was, however, a 50% decrease in CD4+ cells evaluated 24 hr after immunization with sheep red blood cells which persisted for the 5-day culture period. T and B cells were isolated and analyzed for proliferative capacity in response to various mitogenic stimuli. Isolated B cells exhibited no difference between VH- and GaAs-exposed cells in proliferative capacity to either lipopolysaccharide or anti-immunoglobulin plus interleukin-4. However, isolated T cells exposed to GaAs were significantly suppressed in their ability to proliferate to concanavalin A, phytohemagglutinin and anti-CD3 epsilon plus interleukin-2 when compared to VH. In addition, expression of CD25, leukocyte function antigen-1 and intercellular adhesion molecule-1 in GaAs-exposed mice were significantly below VH (36, 18 and 18%, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Gallium arsenide selectively inhibits T cell proliferation and alters expression of CD25 (IL-2R/p55). 809 42

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

We have examined the role of cell adhesion molecules in the homotypic aggregation of rat alveolar macrophages after exposure to wool and grain dusts. Molecules such as bacterial lipopolysaccharide (LPS) and phorbol myristate acetate (PMA) can upregulate adhesion molecules, resulting in aggregation of lymphocytes. In rats treated intratracheally with an inspirable sample of wool dust collected from the air of British wool textile mills, and sieved grain dust, aggregates of macrophages were present in the bronchoalveolar lavage (BAL). Our hypothesis was that substances present on the dust surface could activate and upregulate adhesion molecules of the CD11/CD18 complex on the BAL cells and account for the aggregates. Macrophages from untreated rats form aggregates in vitro, which averaged 19 cells/aggregate; when treated with both wool and grain dusts, this rose to 25 and 24 cells/aggregate, respectively. LPS, PMA, and the proinflammatory cytokine tumor necrosis factor (TNF) also caused increases in aggregate size. Staurosporine, an inhibitor of protein kinase C (PKC), reduced the number of cells per aggregate from 35 cells/aggregate in LPS- and PMA-treated macrophages to 18 cells/aggregate, the same as untreated. In contrast, staurosporine had no effect in reducing the size of aggregates produced by the organic dusts. Removal of divalent cations, which are essential for maintaining integrin stability and PKC activity, resulted in complete abolition of aggregate formation. Treatment with monoclonal antibodies to lymphocyte function-associated antigen-1 (LFA-1) alpha and beta and intercellular adhesion molecule-1 (ICAM-1) resulted in the inhibition of aggregate formation in a dose-dependent manner.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:LFA-1 and ICAM-1 in homotypic aggregation of rat alveolar macrophages: organic dust-mediated aggregation by a non-protein kinase C-dependent pathway. 810 15

We describe the production and characterization of a novel monoclonal antibody (MAb) that recognizes a human endothelial cell antigen expressed mainly in inflamed and malignant disease states. We have used immunohistochemistry to determine the spectrum of reactivity of this MAb compared with that of a MAb to factor VIII-related antigen (MAb FVIII). MAb 4A11 does not react with several myeloid or lymphoid cell lines or with peripheral blood cells. Unlike MAb FVIII, MAb 4A11 does not react with platelets. MAb 4A11 reacts with most vascular endothelial cells in lymphoid tissue but with few (< 10%) endothelial cells in thymus, spleen, liver, lung, adrenal gland, placenta, testes, and skin. MAb 4A11 detects endothelial cells in diseased tissues such as rheumatoid and osteoarthritic synovium and psoriatic skin. Vascular endothelial cells in both adrenal tumors and cutaneous Kaposi's sarcomas lesions are MAb 4A11 reactive. In vitro the 4A11 antigen is not detectable on cultured human umbilical vein endothelial cells and its expression is not induced on these cells by treatment with lipopolysaccharide, interferon-gamma, interleukin-1 and -6, or tumor necrosis factor-alpha. However, in an in vivo model of allergic contact dermatitis the 4A11 antigen is upregulated differentially from other endothelial markers such as E-selectin, vascular cell adhesion molecule-1, and intercellular adhesion molecule-1. In this dermal model of inflammation, poison ivy extract is applied to the skin and biopsies taken at 0, 6, and 24 hours. In addition to focal keratinocyte expression, 4A11 antigen is found on 11% of dermal endothelial cells at time 0 and antigen expression increases with time until 24 hours, when 4A11 antigen is present on 63% of the endothelial cells. Using thin layer chromatography, MAb 4A11 reacts with the H-5-2 [Fuc alpha 2Gal beta 4GlcNAc beta 3Gal beta 4Glc beta 1Cer] and Lewis(y)-6 [Fuc alpha 2Gal beta 4(Fuc alpha 3)GlcNAc beta 3Gal beta 4-Glc beta 1Cer] blood group glycolipids. The presence of the novel 4A11 antigen in inflamed and malignant tissues containing many blood vessels and its differential upregulation in allergic contact dermatitis may signify an important function for this antigen in the inflammatory process.
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PMID:4A11, a monoclonal antibody recognizing a novel antigen expressed on aberrant vascular endothelium. Upregulation in an in vivo model of contact dermatitis. 831 Nov 12

We examined the effect of agents which augment intracellular levels of cyclic adenosine monophosphate on the expression of adhesion molecules on human umbilical vein endothelial cells. Surface protein expression of vascular cell adhesion molecule-1, endothelial leukocyte adhesion molecule-1, or intercellular adhesion molecule-1, which is induced by tumor necrosis factor, interleukin-1, and lipopolysaccharide, was not induced by pentoxyfilline, a phosphodiesterase inhibitor, nor by dibutyryl cyclic adenosine monophosphate. Furthermore, neither of these two cyclic adenosine monophosphate elevating agents nor HA 1004, an inhibitor of the cyclic adenosine monophosphate-dependent protein kinase, had any effect on tumor necrosis factor-alpha-induced surface expression of these adhesion molecules. Likewise, cyclic adenosine monophosphate elevating agents were without effect on leukocyte adherence to endothelium stimulated either with these agents alone or in combination with tumor necrosis factor-alpha. Additionally, activators of the stimulatory or inhibitory guanine nucleotide-dependent binding proteins did not affect TNF-alpha-induced surface expression of endothelial leukocyte adhesion molecule-1 or vascular cell adhesion molecule-1.
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PMID:Cytokine-induced adhesion molecule expression on human umbilical vein endothelial cells is not regulated by cyclic adenosine monophosphate accumulation. 839 31

We investigated the activity of endogenous nucleoside 5'-deoxy-5'-methylthioadenosine (MTA) on both the production of inflammatory cytokines and the cytokine-dependent endothelial expression of adhesion molecules. The compound inhibited the production of tumor necrosis factor (but not interleukin-1) in lipopolysaccharide-activated macrophages. In addition, MTA selectively inhibited the expression of intercellular adhesion molecule-1 in endothelial cells activated with interleukin-1. This effect was paralleled by a reduction in endothelial adhesiveness for polymorphonuclear leukocytes. These data suggest that MTA might have anti-inflammatory activity.
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PMID:Inhibition of cytokine production and endothelial expression of adhesion antigens by 5'-methylthioadenosine. 846 64

Human intercellular adhesion molecule-1 (ICAM-1), a transmembrane glycoprotein that functions as a ligand for lymphocyte function-associated antigen-1, plays an important role in mediating cell-cell interactions in inflammatory reactions. It is induced by proinflammatory cytokines such as interleukin-1, tumor necrosis factor-alpha or interferon-gamma, as well as by phorbol esters, retinoic acid and lipopolysaccharide. Furthermore, ICAM-1 is upregulated by interleukin-6, which suggests that it belongs to the family of acute phase response genes. Investigation of the 5'-regulatory region of the human ICAM-1 gene revealed sequence motifs for a variety of transcription factors implicated in transcriptional regulation. This review summarizes the current knowledge of the transcriptional regulation of the human ICAM-1 gene.
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PMID:Transcriptional regulation of the human intercellular adhesion molecule-1 gene: a short overview. 853 Jan 58

The influence of lipopolysaccharide (LPS) and various cytokines on the expression of the costimulatory molecule B7-1 and intercellular adhesion molecule-1 (ICAM-1), lymphocyte function associated antigen-3 (LFA-3) and human histocompatibility leucocyte antigen-DR (HLA-DR) on human monocytes and their effect on the costimulatory function was investigated. Freshly isolated human monocytes constitutively express ICAM-1, LFA-3 and HLA-DR, but no B7-1. B7-1 expression was up-regulated by LPS and, to a lesser extent, by interferon-gamma (IFN-gamma). The other stimuli tested, including IFN-alpha, granulocyte-macrophage colony-stimulating factor (GM-CSF), tumour necrosis factor-alpha (TNF-alpha) and GM-CSF+TNF-alpha, did not influence expression of B7-1 on monocytes. ICAM-1 and HLA-DR were up-regulated by IFN-gamma and LPS; LFA-3 expression was not influenced. LPS also effectively enhanced costimulatory function of monocytes as determined in the tetanustoxoid (TT) assay. Blocking of B7 by CTLA-4Ig inhibited the LPS-induced enhancement of costimulatory function almost completely. Our results indicate that the LPS-mediated up-regulation of the costimulatory function of human monocytes is mediated by B7. This mechanism may be important for host defence against Gram-negative bacteria.
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PMID:Lipopolysaccharide effectively up-regulates B7-1 (CD80) expression and costimulatory function of human monocytes. 855 95

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