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)

Explants of bovine articular cartilage were cultured for up to 50 days in 20% fetal calf serum in the presence or absence of the endotoxin lipopolysaccharide (LPS); or in various protocols involving different treatment times with LPS followed by recovery times in the absence of LPS. Cultures were measured in terms of rates of proteoglycan synthesis (incorporation of [35S]sulfate), proteoglycan contents and collagen contents. Histological sections were prepared for both light and electron microscopy. In fetal calf serum, the rates of synthesis and contents of proteoglycans per collagen remained constant, while for LPS treated cultures both parameters decreased. For recovery groups, the rates of proteoglycan synthesis increased during the time of recovery if the LPS treatment times were relatively short (2 weeks or less) and if the tissue was obtained from younger animals; net increase in proteoglycan contents occurred infrequently if at all during recovery protocols. Histological examinations revealed that chondrocytes in cultures maintained in fetal calf serum appeared normal with large stores of glycogen. In LPS treated cultures, chondrocytes were depleted of glycogen stores and contained numerous lipid droplets. In recovery cultures, chondrocytes replenished their glycogen contents, but the lipid droplets remained. For both LPS treated and recovery groups the extracellular matrix was depleted of proteoglycans with time in culture. The results provide further evidence for the ability of this explant culture system to maintain steady state metabolic parameters for proteoglycan metabolism over long time periods and for its utility to study reagents which regulate or perturb these parameters.
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PMID:Biochemical and morphological studies of steady state and lipopolysaccaride treated bovine articular cartilage explant cultures. 280 82

Stimulated T lymphocytes and certain T-cell hybridomas secrete molecules capable of inducing B-lymphocyte proliferation and differentiation. It has been shown recently that one such B-cell stimulatory factor is associated with chondroitin sulphate proteoglycan (CSPG) and was designated T-cell proteoglycan fraction, or T-PGF. We report here that mouse spleen cells cultured at high densities or stimulated with lipopolysaccharide (LPS) at low cell densities secrete antibodies directed against T-PGF. Such antibodies react primarily with the CSPG component of T-PGF and can inhibit the induction of plaque-forming cells (PFC) by T-PGF. By fusing high-density cultures of unstimulated mouse spleen cells with the myeloma P3 x 63AG8.653, several anti-T-PGF (CSPG) hybridomas were derived that exhibited activities identical to anti-T-PGF (CSPG) obtained from high-density spleen cell culture supernatants. The role that these spontaneously secreted autoantibodies may play in immunoregulation is discussed.
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PMID:Naturally occurring mouse antibodies against T-cell-secreted chondroitin sulphate proteoglycan. 304 20

The effect of lipopolysaccharide preparations from Salmonella enteritidis, Bacteroides gingivalis, and Actinobacillus actinomycetemcomitans on human gingival fibroblasts was studied. Lipopolysaccharide from all sources inhibited fibroblast proliferation in the concentration range of 0.5 to 50 micrograms/ml, with the lipopolysaccharide from A. actinomycetemcomitans having the strongest inhibitory effect. Assessment of the effect of lipopolysaccharide on gingival fibroblast metabolism indicated both total protein and proteoglycan synthesis to be inhibited with increasing concentrations of lipopolysaccharide. As for the antiproliferative effect, lipopolysaccharide from A. actinomycetemcomitans had the greatest inhibitory effect on cell synthetic activity. This inhibitory effect was determined by pulse-chase experiments to be a true depression in synthesis. Furthermore, the effect was independent of lipopolysaccharide-induced changes in cell proliferation and prostaglandin synthesis. This study confirmed the toxic effect of lipopolysaccharide on fibroblasts and, in particular, indicated that various lipopolysaccharide preparations vary in their potency to influence cell proliferation and extracellular matrix synthesis.
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PMID:Effect of lipopolysaccharide on proteoglycan synthesis by adult human gingival fibroblasts in vitro. 316 85

We compared the distribution of fibronectin and chondronectin within the matrix of canine articular cartilage. Fibronectin was found throughout the matrix as well as pericellularly. In contrast, chondronectin was observed predominantly associated with the cell or pericellular matrix. Interactions of these molecules with matrix components in the pericellular matrix probably differs, however, since concentrations of hyaluronidase which prevented detection of pericellular fibronectin allowed detection of chondronectin. Chondronectin and fibronectin were detected in osteoarthritic cartilage as well as in disease-free cartilage. Penetration of biotinylated fibronectin into cartilage from the external medium occurred only in osteoarthritic cartilage and proceeded only from the articular surface. Disease-free cartilage appeared to maintain a barrier to fibronectin penetration from the articular surface which was sustained even after the proteoglycan content was markedly depleted by incubation of cartilage with catabolin or lipopolysaccharide. In cartilage that was proteoglycan-depleted, the only detectable penetration of external fibronectin was from the cut surface.
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PMID:Immunohistochemical localization of fibronectin and chondronectin in canine articular cartilage. 328 48

The effect of conditioned media from Kupffer cells of normal, D-galactosamine- and thioacetamide-treated rats on the synthesis of proteoglycans by rat liver fat-storing cells in culture was studied in order to elucidate some of the mechanisms initiating enhanced connective tissue proteoglycan synthesis in injured liver. The incorporation of [35S]sulfate and [3H]glucosamine into proteoglycans was 2.1-2.5 fold (P less than 0.005) stimulated by the additions of normal, D-galactosamine- and thioacetamide-exposed Kupffer cell media. The concentrations of hexuronic acid and amino sugars in the medium glycosaminoglycan fraction were enhanced 5-fold and 4.5-fold, respectively, if the fat-storing cells were cultured in the presence of normal Kupffer cell conditioned medium. Treatment of normal Kupffer cells in culture with zymosan and phorbol esters, but not the addition of lipopolysaccharide, enhanced further the proteoglycan synthesis-stimulating effect of normal (untreated) Kupffer cells. The pattern of newly formed [35S]sulfate-labeled proteoglycans was changed in the presence of Kupffer cell media, showing a strong fractional increase of chondroitin sulfate and a relative decrease of dermatan sulfate, but the fraction of heparan sulfate was almost unaffected. In absolute terms Kupffer cells stimulated the total (medium and cell fraction) synthesis of chondroitin sulfate 2.8-fold and that of dermatan sulfate 1.5-fold. Although the DNA content of fat-storing cell cultures was increased by incubation with Kupffer cell media, an enhancement of proteoglycan synthesis was also observed when related to the DNA content of the cultures. The stimulation of proteoglycan synthesis was not dependent on the induction of cell proliferation. Gel chromatography and beta-elimination of medium proteoglycans revealed no changes of the molecular weight distribution profile of native proteoglycans and glycosaminoglycan chains synthesized under the influence of the various Kupffer cell media. Activation of proteoglycan synthesis and secretion in fat-storing cells by Kupffer cell-derived factor(s) might be an important mechanism of their strong accumulation in the connective tissue of fibrotic livers.
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PMID:Kupffer cell-mediated induction of synthesis and secretion of proteoglycans by rat liver fat-storing cells in culture. 342 38

Articular cartilage explants from the knees of mongrel dogs release 5-10% of their proteoglycan content spontaneously when cultured for 4 days in serum-free modified Bigger's medium. A factor synthesized and secreted by lipopolysaccharide-stimulated rabbit macrophages can stimulate this release of proteoglycan by 2 to 3-fold. The release of proteoglycan in response to macrophage factor is maximal in the presence of 1.5-50 micrograms/ml L-ascorbic acid. In the absence of ascorbate, or with high levels of ascorbate (150 micrograms/ml), the effect of the factor is diminished by 50%. D-isoascorbate, reduced glutathione, or dithiothreitol cannot substitute for L-ascorbate in producing this effect, while dehydroascorbate can.
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PMID:Ascorbic acid stimulates the resorption of canine articular cartilage induced by a factor derived from activated rabbit macrophages. 392 38

The ability of mononuclear leukocytes to synthesize and secrete proteoglycans was evaluated. Using radiolabeling with H2 35SO4, it is shown that peripheral blood mononuclear cells (PBMC) and their major subpopulations (B cells, T cells, and monocytes), as well as mouse spleen cells, all secreted easily detectable proteoglycan. After 24-h labeling periods, 90% of macromolecular 35S could be detected in culture media. This material was primarily (greater than 95%) chondroitin-4-sulfate proteoglycan (CSPG). Production and secretion of CSPG could be stimulated more than 200% in PBMC and 300% in T cell populations by high concentrations of concanavalin A and phorbol 12-myristate-13-acetate; lipopolysaccharide induced a small (twofold) but reproducible increase in CSPG secretion by adherent mononuclear leukocytes. The CSPG secreted by PBMC was relatively small in size compared to chondrocyte CSPG (130,000 daltons vs. 2-4 million daltons) but possessed similar sizes of glycosaminoglycan chains and greater solubility in low ionic strength solutions. This sulfated polyanion, which was produced endogenously by leukocytes and was actively secreted, might function as a co-mediator or "second messenger" in certain immune responses.
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PMID:Induction of chondroitin sulfate proteoglycan synthesis and secretion in lymphocytes and monocytes. 660 59

We investigated whether stromelysin activity in the medium of canine articular cartilage explants is associated with proteoglycan degradation in these explants. Cartilage explants were treated with recombinant human interleukin 1 alpha (rh-IL-1 alpha), lipopolysaccharide, or canine monocyte-conditioned medium. Proteoglycan synthesis and degradation were measured. Metalloproteinase activity (inhibitable by tissue inhibitor of metalloproteinase 2) in the culture medium was measured by use of fluorimetry with a quenched fluorescent substrate. Western blots of the medium were probed with polyclonal antibodies to human stromelysin, collagenase, and gelatinase. Neither metalloproteinase activity nor proteoglycan degradation were inducible in canine cartilage explants treated with rh-IL-1 alpha. However, proteoglycan synthesis was significantly (P < 0.05) decreased by concentrations of 10 and 100 ng of rh-IL-1 alpha/ml. Metalloproteinase activity in the medium accompanied proteoglycan degradation of cartilage treated with lipopolysaccharide and monocyte-conditioned medium. The metalloproteinase released into the medium was identified as prostromelysin by results of western blotting.
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PMID:Effects of stromelysin activity on proteoglycan degradation of canine articular cartilage explants. 748 6

Plasminogen activator inhibitor-1 (PAI-1) is a primary endogenous inhibitor of tissue-type plasminogen activator (t-PA). In this study, we examined the effects of oversulfated fucoidan (OSF) derivatives and heparin on lipopolysaccharide (LPS)-induced release of PAI-1 antigen from cultured human umbilical vein endothelial cells (HUVEC). Addition of LPS (10 micrograms/ml) enhanced the release of PAI-1 by HUVEC but not of t-PA antigen. At 18 h, a 2.4-fold increase in the extracellular PAI-1 level was observed. The increased PAI-1 level was reduced to control level by the simultaneous addition of 10 micrograms/ml of OSF or heparin. The suppressive effect of native fucoidan was negligible. We also examined the molecular size effect of OSF, using 10-20, 20-40, and 40-60 kDa fragments. The result indicated that these fragments were effective as well as the 100-130 kDa form of OSF, hence suggesting an important role of the degree of sulfation. Interleukin-1 beta (IL-1 beta) is a potent inducer of PAI-1 in cultured HUVEC. Heparin, OSF, and its fragments did not suppress the IL-1 beta-induced release of PAI-1 antigen. Treatment of HUVEC with heparitinase or monoclonal antibody against heparin sulfate proteoglycan (HSPG) resulted in a complete loss of its ability to enhance PAI-1 release in response to LPS stimulation, while the chondroitinase ABC treatment hardly affected the PAI-1 production. These results suggest that HSPG is involved in the initial binding of LPS to HUVEC. The suppressive effects of OSF and heparin on LPS-induced PAI-1 release may result from the inhibition of LPS binding to the cell surface HSPG.
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PMID:Oversulfated fucoidan and heparin suppress endotoxin induction of plasminogen activator inhibitor-1 in cultured human endothelial cells: their possible mechanism of action. 757 76

The expression of many genes is altered upon the activation of macrophages by bacterial LPS. These genes play a crucial role in the orchestration of various responses to protect the host against infection. A novel 2.3 kilobase (kb) cDNA, designated IRG1, was obtained from a cDNA library prepared with RNA isolated from RAW 264.7 following lipopolysaccharide stimulation. Sequence analysis of the clone revealed no identity to any known genes but showed the presence of many potential phosphorylation sites suggesting that IRG1 protein product may be regulated at this level. Furthermore, IRG1 contains the motif for glycosaminoglycan attachment site, implying that IRG1 may be a proteoglycan. By interspecific back-cross analysis, Irg1 was mapped to mouse chromosome 14 linked to Tyrp2 and Rap2a. The IRG1 message appears 1.5 h following LPS exposure and its induction was not dependent on new protein synthesis. In fact, cycloheximide induced the expression of IRG1, suggesting that a protein repressor prevents the expression of IRG1 when uninduced. The role of the protein kinase A pathway in regulating the induction of IRG1 by LPS is questionable, because although forskolin inhibited its induction, neither dibutyrl-cAMP nor 8-(4-chlorophenylthio)-cAMP had much effect on its expression. In contrast, activation of protein kinase C potentiated the LPS response. Chelation of extracellular calcium inhibited IRG1 4 h after LPS induction, while increasing intracellular calcium had little effect on the levels of the IRG1 transcript. Inhibiting tyrosine phosphorylation abrogated the induction of IRG1 by LPS. Hence, the induction of IRG1 by LPS is mediated by tyrosine kinase and protein kinase C pathway.
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PMID:Cloning and analysis of gene regulation of a novel LPS-inducible cDNA. 772 48


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