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)

Nitric oxide (NO) is an important effector molecule of the inflammatory response. It is synthesized by mesangial cells and has been proposed to contribute to glomerular injury in various disease states. We studied whether NO modulates extracellular matrix production in cultured rat mesangial cells. Stimulation of rat mesangial cell NO release with gamma-interferon and lipopolysaccharide resulted in reduced production of collagen (by 35%) fibronectin (by 48%) (P < 0.05). In contrast, laminin synthesis was enhanced two-fold by the same maneuver (P < 0.05). These changes were reversed by the addition of L-NAME, a selective inhibitor of inducible nitric oxide synthase. This is the first demonstration that NO regulates the synthesis of extracellular matrix by mesangial cells. The results indicate that increased renal production of NO in glomerular diseases may attenuate the production and accumulation of matrix proteins and limit the severity of glomerulosclerosis.
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PMID:Nitric oxide modulates the synthesis of extracellular matrix proteins in cultured rat mesangial cells. 785 53

We have previously reported that culture of human peripheral blood leukocytes with interleukin-2 (IL-2) triggers the secretion of mediators which induce fibroblast proliferation and collagen synthesis. In addition, fibrogenic cytokines (transforming growth factor-beta 1 (TGF beta 1) and platelet-derived growth factor (PDGF) A and B chain) are present in the peritoneal fluid of patients undergoing intraperitoneal immunotherapy (IL-2-activated killer cells and IL-2) who go on to develop peritoneal adhesions. To determine the role of IL-2 in the formation of these adhesions, we chose to investigate whether IL-2 can induce the expression of fibrogenic cytokine genes in resident rat peritoneal macrophages. Cells were cultured with or without IL-2 or lipopolysaccharide (LPS) and expression of PDGF A chain, PDGF B chain, and TGF beta 1 mRNAs was determined. PDGF A and B chain mRNAs are minimally expressed in macrophages prior to stimulation and are induced within 2 hours of treatment with IL-2. In contrast, TGF beta 1 mRNA is constitutively expressed and can not be upregulated. The studies suggest that peritoneal macrophage-derived PDGF plays a critical role in the production of adhesions in patients receiving intra-abdominal immunotherapy.
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PMID:Selective induction of PDGF gene expression in peritoneal macrophages by interleukin-2. 808 55

The objective of this study was to investigate food restriction-related changes in several indices of immune competence in young (11 wk old) and adult (33 wk old) female lean (+/?) and obese (ob/ob) C57BL/6J mice. Body weight accumulation, tail length accretion and organ weights were more severely curtailed by food restriction in obese mice than in lean mice. Tail collagen denaturation time increased with age, although the magnitude was greater in obese mice, and this change was minimized by food restriction. Splenocyte mitogen responses were generally not altered with age in lean or obese mice, whereas food restriction augmented these responses in lean mice while having no effect or reducing them in obese mice. The concanavalin A and phytohemagglutinin responses of splenocytes from young and adult obese mice were greater than those for lean mice, whereas the bacterial lipopolysaccharide response was elevated only in adult obese vs. lean mice. Flow cytometric analysis of splenocytes revealed an increase in Thy-1+ cells with food restriction vs. freely fed obese and lean mice, with a proportional decrease in Ig+ cells. Percentages of CD4+ and CD8+ cells increased with food restriction in both lean and obese mice. These results suggest that genetic obesity largely eliminates the immunopotentiating effects of food restriction, although the rate of "aging" may be reduced by food restriction.
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PMID:Obesity minimizes the immunopotentiation of food restriction in ob/ob mice. 808 31

The effect of endotoxic lipopolysaccharide (LPS) on platelet shape change (PSC; a preaggregation event) was investigated. PSC is accompanied by an increase in median platelet volume (MPV), which was measured using a channelyzer. In whole blood, but not in platelet rich plasma (PRP), LPS (final concentration 80 mg/l) caused an increase in MPV that could be detected for 2 h. When PRP (prepared from LPS- and saline-pretreated whole blood) was incubated for 40 min, the LPS-mediated increase in MPV could no longer be detected. Taken together, these data imply that PSC is both initiated and maintained by a labile factor(s) present in whole blood, but not in PRP. PRP was prepared from LPS-pretreated whole blood and incubated for 40 min to allow reversal of the LPS-induced PSC; further stimulation with LPS caused PSC. Platelets from LPS-pretreated whole blood also showed enhanced PSC with serotonin (5-HT), diminished PSC with platelet activating factor (PAF), and no change of response to ADP and collagen. Hence, LPS pretreatment of whole blood differentially alters responses of platelets to further stimulation with LPS and other agonists. A specific PAF antagonist completely abolished the effect of LPS on MPV. These data may contribute to an understanding of the cascading thrombotic events and thrombocytopenia associated with septicaemia.
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PMID:Platelet shape change in whole blood: differential effects of endotoxin. 809 94

Massive hepatic cell necrosis can be induced by Corynebacterium parvum and lipopolysaccharide (LPS) in rats. In this model, serum LDH, GOT and GPT activities are significantly increased in vivo within several hours after LPS injection. An in vitro experimental acute liver injury animal model was produced by using multicellular spheroids composed of rat parenchymal and non-parenchymal liver cells. These multicellular spheroids were prepared by detaching the confluent monolayer on the collagen-conjugated thermo-responsive polymer coated culture dish at a temperature below the lower critical solution temperature and culturing it on the non-adhesive substratum. LPS caused clear elevations of GOT, GPT and LDH activities from these spheroids into the medium. However, the increase of LDH activity was only observed in the monolayer culture system. These results suggest that the multicellular spheroids of liver cells are useful models as an alternative to animal tests for hepatotoxicity.
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PMID:An experimental model of acute liver injury using multicellular spheroids composed of rat parenchymal and non-parenchymal liver cells. 812 32

In this study we demonstrate that adherence of peripheral blood mononuclear cells (PBMC) to either plastic or extracellular matrix, such as collagen type I or fibronectin, is a significant stimulus for the induction of both interleukin-8 (IL-8) mRNA and antigen. In addition, adherence of PBMC in the presence of lipopolysaccharide, interleukin-1-beta, or tumor necrosis factor-alpha greatly enhances transcription/translation of IL-8 from these leukocytes. Our findings demonstrate that PBMC adherent to either plastic or physiological surfaces in combination with an inflammatory agonist is both a potent and efficacious signal for the expression and production of the neutrophil chemotactic/activating cytokine, IL-8.
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PMID:Adherence in combination with lipopolysaccharide, tumor necrosis factor or interleukin-1 beta potentiates the induction of monocyte-derived interleukin-8. 821 28

The production of collagen-degrading proteases by cultured neonatal rat microglia was examined using an immobilized fibronectin-gelatin matrix coupled to a fluorescent marker and by substrate gel analysis. When microglia were plated onto the surface of the matrix and incubated under resting (nonstimulated) conditions, a small but visible amount of immobilized matrix was degraded. Treatment with lipopolysaccharide (LPS) or interleukin-1 (IL-1) significantly increased the number of microglia demonstrating substrate degradation. Substrate-SDS polyacrylamide gel electrophoresis of samples of supernatants from untreated cultured microglia indicated the presence of a 72 and a 92 kD metalloproteinase with characteristics corresponding to collagenases. Supernatants from untreated astrocyte cultures were shown to have primarily a 72 kD metalloproteinase. Proteinase activity increased on stimulation of the microglia with LPS and IL-1 in a dose-dependent fashion. These results indicate that cultured microglia release active proteases capable of degrading the extracellular matrix in a localized region. The production of proteases by activated microglia may have important physiological and pathophysiological consequences within the restricted extracellular matrix of the CNS.
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PMID:Protease production by cultured microglia: substrate gel analysis and immobilized matrix degradation. 835 Mar 90

Patients with human immunodeficiency virus (HIV) infection are prone to the development of focal segmental glomerulosclerosis, a lesion in which increased mesangial cell proliferation and matrix synthesis may play a role. We undertook the present study to determine whether HIV sera may affect mesangial cell proliferation and matrix synthesis either directly or indirectly via effects on macrophage supernatants. Pooled HIV sera was found to significantly enhance (P < 0.01) mesangial cell proliferation in a concentration-related manner. Mesangial cell proliferation was significantly suppressed by two medications commonly utilized in HIV-infected patients, azidothymidine and trimethoprim/sulfamethoxazole, and was not significantly altered by lipopolysaccharide, suggesting that these medications as well as recurrent infection are unlikely to account for the proliferative effect of HIV sera. Supernatants from HIV sera-treated macrophages were found to significantly enhance (P < 0.01) mesangial cell incorporation of [3H]proline, a marker for synthesis of the matrix component collagen, compared to supernatants from control sera-treated macrophages. These results suggest that HIV sera may directly enhance mesangial cell proliferation and may indirectly increase mesangial cell matrix synthesis by altering macrophage secretory products. These effects may play a role in the development of glomerulosclerosis in patients with HIV infection.
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PMID:Effects of human immunodeficiency virus sera and macrophage supernatants on mesangial cell proliferation and matrix synthesis. 836 79

The emigration of peripheral blood monocytes into the interstitium allows for contact with a variety of surfaces which may provide signals important for monocyte function in both normal and inflammatory states. In the present study, we examined the effect of adherence to an endothelial cell-derived basement membrane and to collagen I, the major collagen of the interstitium, on monocyte release and gene expression of the potent chemotactic cytokine Interleukin-8 (IL-8). We further evaluated neutrophil chemotactic activity of the conditioned media containing antigenic IL-8 from monocytes adherent to these same surfaces. Elutriation-purified monocytes were adhered for 1 hour to plastic tissue culture wells either uncoated (PL) or coated with bovine serum albumin (BSA), collagen type I (C-I), or endothelial cell-derived basement membrane (BM). Following removal of nonadherent cells, monocytes were further incubated in a serum-free media for 18 hours in the presence or absence of lipopolysaccharide (IPS). Following 18 hrs of incubation there were significantly less monocytes remaining adherent to BM when compared to other surfaces tested. In the absence of LPS, adherent monocytes released significant amounts of IL-8 that was not surface specific. In the presence of LPS, monocytes adherent to BM released significantly more IL-8, when corrected for adherent cell number, than monocytes adherent to PL, BSA, or C-I. Conditioned media from adherent monocytes expressed IL-8 dependent neutrophil chemotactic activity that was not influenced by the surfaces tested. Northern blot analysis indicated greater induction for IL-8 mRNA by monocytes adhered to BM after 18 hrs in the presence of LPS. These results suggest that monocyte adherence to the subendothelial basement membrane provides a priming signal for the induction and secretion of the chemotactic cytokine IL-8 in response to inflammatory stimuli.
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PMID:Monocyte adherence to the subendothelial basement membrane increases interleukin-8 gene expression and antigen release. 854 67

Binding of outer membrane (OM) preparations of the thermophilic Campylobacter species C. jejuni to epithelial cell membranes and extracellular matrix proteins were studied in an in vitro model system using enzyme-linked immunosorbent assay. The OM preparations exhibited significant binding to INT 407 intestinal cell membranes. The process of adhesion was modulated by enzymatic, chemical or immunological pretreatment of the bacteria. Following oxidation of the lipopolysaccharide (LPS) with sodium meta-periodate, the OM preparations essentially retained their binding properties. After pretreatment with proteinase K, the OM preparations lost their binding capacity and the apparent molecular mass of the major OM protein shifted from 42 to 24 kDa. Preincubation of C. jejuni bacteria with C. jejuni-specific antiserum reduced adhesion significantly; preincubation with LPS-specific monoclonal antibodies only to a minimal extent. The OM preparations also bound significantly to the extracellular matrix proteins collagen and fibronectin; however, they bound virtually no bovine serum albumin or horse serum.
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PMID:Binding of outer membrane preparations of Campylobacter jejuni to INT 457 cell membranes and extracellular matrix proteins. 857 16


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