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)

Tumor necrosis factor alpha (TNF alpha) and thromboxane A2 (TXA2) are major products of the activated alveolar macrophage and serve as key mediators of lung injury. In order to determine if the synthesis of TXA2 and the release of TNF alpha are associated, the production of these inflammatory agents by the human alveolar macrophage (AM), as a result of activation by lipopolysaccharide (LPS), was assessed in the absence and presence of the thromboxane synthase inhibitors UK 38,485 (Dazmegrel) and OKY 046. UK 38,485 and OKY 046 inhibited both LPS-stimulated TXA2 production and TNF alpha release in a dose-dependent manner. Prostaglandin E2 (PGE2) production was not increased by UK 38,485 or OKY 046. Neither LPS nor UK 38,485 had any effect on LTB4 production by AM. Neither UK 38,485 or OKY 046 had any effect on LPS-stimulated interleukin-1 beta release. However, the TXA2 mimetic, U46619, did not stimulate TNF alpha release by AM either in the absence or presence of UK 38,485. These findings suggest that 1) UK 38,485 and OKY 046 are inhibitors of both TXA2 production and TNF alpha release by activated human AM, 2) UK 38,485 probably does not exert its inhibitory action on TNF alpha release through effects on eicosanoid production and 3) the possibility that TNF alpha- and TXA2-induced lung injury may be subject to amelioration by imidazole-based compounds should be further evaluated.
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PMID:An inhibitor of thromboxane production attenuates tumor necrosis factor release by activated human alveolar macrophages. 823 28

We examined the effect of infusion of lipopolysaccharide (LPS) on serum tumor necrosis factor alpha (TNF alpha) concentration and clinical attitude in 2- 3-day-old colostrum-fed (CF) and colostrum-deprived (CD) foals. Eleven CF and 8 CD neonatal foals were given a bolus i.v. infusion of Escherichia coli O55:B5 lipopolysaccharide (0.5 microgram/kg of body weight) in sterile saline (0.9% NaCl) solution. Four CF and 2 CD foals were given saline solution alone. Serum IgG concentration and serum anti-LPS IgG(T) antibody titer were determined for each foal prior to infusion. A depression index was used to score clinical abnormalities. Serum TNF alpha concentration was estimated by use of an in vitro cytotoxicity bioassay that used WEHI 164 clone 13 cells as targets. The cytotoxic serum factor was identified as TNF alpha by immunoprecipitation with caprine antisera raised against the 15 NH2-terminal amino acids of human TNF alpha. Tumor necrosis factor alpha was not detected in any preinfusion serum samples nor in any samples from foals given saline solution alone. Serum TNF alpha concentration increased in all LPS-infused foals and peaked between 60 and 90 minutes after infusion. Serum TNF alpha concentrations, expressed as mean percentage of peak serum TNF alpha concentration, persisted longer in CD foals given LPS than in CF foals given LPS. All LPS-infused foals displayed clinical signs of endotoxemia, but mean depression index scores of the CF and CD foals given LPS were not significantly different at any time. Serum TNF alpha concentrations were correlated with depression index scores in both LPS-infused groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Serum tumor necrosis factor alpha concentrations and clinical abnormalities in colostrum-fed and colostrum-deprived neonatal foals given endotoxin. 823 25

Endotoxins (lipopolysaccharide, LPS) are biologically active substances present in Gram-negative bacteria. Injection of purified LPS into experimental animals leads to the development of many biological activities that can lead to shock with lethal outcome. The biological activities of LPS are not direct effects of the LPS molecule since LPS usually expresses no direct cytotoxic activity. The toxic and other biological properties of LPS are caused indirectly through the action of endogenous mediators that are formed following interaction of LPS with cellular targets, macrophages occupying a key position in the development of endotoxin shock. The interaction of LPS with macrophages may proceed directly leading to activation of these cells, with subsequent synthesis and secretion of a number of endogenous mediators which initiate the different biological activities of LPS. Tumor necrosis factor alpha (TNF-alpha), a macrophage derived cytokine, is a primary mediator of the lethal action of endotoxin. Sensitivity to LPS is genetically determined, varying considerably among different species. The sensitivity of normal animals (mice) to endotoxin may be enhanced considerably under different experimental conditions that include treatment with live (infection) or killed Gram-negative and -positive bacteria. Sensitization to endotoxin proceeds in all LPS-responder strains investigated and in the LPS-resistant mice of the strain C3H/HeJ. It does not proceed in a second LPS-resistant strain, C57BL/10ScCr. The absence of sensitization in the latter mice was found to be due to an impaired IFN-gamma production. IFN-gamma could be identified as the mediator of endotoxin hypersensitivity induced by bacteria.
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PMID:Mechanisms of endotoxin shock and endotoxin hypersensitivity. 833 Sep 3

Tumor necrosis factor alpha (TNF-alpha) has been shown to be an important mediator of the lethal effects of endotoxin in several experimental models of septic shock. However, studies with a recombinant human interleukin-1 (IL-1) receptor antagonist protein (IL-1ra) suggest a role for IL-1 as a mediator of septic shock as well. In the present study, we show that mice treated in vivo with Corynebacterium parvum are primed for the production of interferon-gamma (IFN-gamma) and exhibit an enhanced capacity to produce serum IL-1 alpha, TNF-alpha, and IL-6 when challenged intravenously with lipopolysaccharide (LPS). The majority of C. parvum-treated mice die within 24 h of an LPS challenge. Pretreatment with a rat antimouse TNF-alpha monoclonal antibody (mAb) protected 90% of the animals against the lethal endotoxin challenge, while an anti-IFN-gamma mAb gave approximately 75% protection. The anti-IFN-gamma mAb also caused a reduction in LPS-induced serum TNF-alpha and IL-1 alpha. Anti-IL-1 alpha, anti-IL-1 beta, and anti-IL-6 neutralizing mAb did not protect against lethality when administered to mice prior to the LPS challenge. These results indicate that TNF-alpha and IFN-gamma are major mediators of endotoxin shock in C. parvum-treated mice. The results further suggest that the IFN-gamma produced by C. parvum-primed mice in response to an LPS challenge serves as a stimulus for enhanced production of TNF-alpha and IL-1 alpha. These findings are consistent with an increasing body of evidence suggesting a major role for IFN-gamma in lethal endotoxemia.
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PMID:Lipopolysaccharide-induced cytokine production and mortality in mice treated with Corynebacterium parvum. 833 76

Tumor necrosis factor alpha (TNF-alpha) is most commonly produced by macrophages stimulated by lipopolysaccharide (LPS). The present study shows that BSA in place of FBS in RPMI 1640 medium accelerated the rate of LPS-induced TNF-alpha production by resident peritoneal macrophages from BALB/c mice when compared to LPS in serum free medium. Using 10 or 100 ng LPS/ml and 100 U IFN-gamma/ml in RPMI 1640 medium plus 0.5% BSA, both cytoplasmic TNF-alpha mRNA and TNF-alpha precursor and extracellular TNF-alpha production by mouse macrophages were increased when compared to stimulation by LPS plus IFN-gamma in medium without BSA and FBS. The level of TNF-alpha produced was shown to be related to the BSA concentration. Medium containing BSA but no LPS also stimulated macrophages to produce TNF-alpha, but BSA's TNF-alpha inducing activity varied among different lots and was not blocked by polyclonal antibody to BSA. This effect appeared to be associated with the presence of immunoglobulin in BSA products. Confirmation that BSA activity was not due to LPS contamination was achieved by testing macrophages from LPS-nonresponder C3H/HeJ mice, as well as testing TNF-alpha induction in the presence of polymyxin B (10 micrograms/ml), an LPS inhibitor.
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PMID:Bovine serum albumin preparations enhance in vitro production of tumor necrosis factor alpha by murine macrophages. 854 38

In vivo administration of Porphyromonas gingivalis lipopolysaccharide (Pg-LPS) to mice induced apoptosis before a specific immune response. Apoptosis was associated with the expression of immunoglobulin and Ia on B cells and of CD5 and several markers on T cells. Apoptosis peaked in the spleen and lymph nodes on day 2, and the second peak occurred in the thymus on day 9. Tumor necrosis factor alpha (TNF-alpha) could mediate apoptosis, because the serum TNF-alpha levels were significantly higher than those of controls at 1 day before apoptosis and recombinant murine TNF-alpha induced apoptosis. The apoptosis induced by Pg-LPS was similar to that induced by Escherichia coli LPS in its basic manner, but it was unique in the response of thymus T cells. It was suggested that Pg-LPS could induce apoptosis for the elimination of early nonspecific activated lymphocytes.
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PMID:In vivo induction of apoptosis and immune responses in mice by administration of lipopolysaccharide from Porphyromonas gingivalis. 860 20

The 170-kDa subunit of the galactose-adherence lectin (Gal-lectin) of Entamoeba histolytica mediates adherence to human colonic mucins and intestinal epithelium as a prerequisite to amebic invasion. The Gal-lectin is an immunodominant molecule and a protective antigen in the gerbil model of amebiasis. Tumor necrosis factor alpha (TNF-alpha) produced by activated macrophages enhances nitric oxide-dependent cytotoxicity in host defense against E. histolytica. The purpose of this study was to identify the Gal-lectin epitopes which stimulate TNF-alpha production by macrophages. Murine bone marrow-derived macrophages (BMMs) exposed to Gal-lectin (100-500 ng/ml) stimulated stable expression of TNF-alpha mRNA (8-fold increase) and TNF-alpha production similar to that of lipopolysaccharide-stimulated cells (100 ng/ml). Polyclonal anti-lectin serum specifically inhibited TNF-alpha mRNA induction in response to the Gal-lectin but not to lipopolysaccharide. Anti-lectin monoclonal antibodies 8C12, H85 and 1G7, which recognize nonoverlapping epitopes of the cysteine-rich region of the 170-kDa heavy subunit, inhibited both amebic adherence to mammalian cells and Gal-lectin-stimulated TNF-alpha mRNA expression by BMMs,but monoclonal antibody 7F4 did neither. As these inhibitory antibodies map to amino acids 596-1082 of the 170-kDa Gal-lectin, our results have identified the functional region that mediates amebic adherence and TNF-alpha mRNA induction in BMMMs; thus, this region of the Gal-lectin is a subunit vaccine candidate.
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PMID:Identification of the galactose-adherence lectin epitopes of Entamoeba histolytica that stimulate tumor necrosis factor-alpha production by macrophages. 861 66

Tumor necrosis factor alpha, in the secreted as well as membrane-associated (mTNF alpha) form, represents a cytotoxic effector mechanism of activated macrophages; in contrast, direct evidence of the mTNF alpha involvement in cytotoxic T lymphocyte (CTL)-mediated lysis has not yet been obtained. We observed that following activation with anti-CD3 monoclonal antibody (mAb), both cloned CTL and peritoneal exudate lymphocytes rapidly upregulated mTNF alpha; a similar effect was observed in the macrophage cell line J774 after stimulation with lipopolysaccharide endotoxin. Activated effector cells, which were fixed with paraformaldehyde before testing, exerted lytic activity against the TNF-sensitive WEHI 164 tumor cell line, but not against the TNF-resistant P-815 mastocytoma. This effect was completely inhibited in the presence of anti-mouse TNF alpha Ab. Moreover, both mTNF alpha-expressing macrophages and CTL induced nuclear DNA fragmentation in WEHI 164 cells, which was also blocked by anti-TNF alpha Ab and was accompanied by a morphologic degeneration characteristic of the apoptotic form of cell death. These data on the whole indicate a common mode of action for mTNF alpha expressed on different cell populations endowed with cytotoxic capability and also imply a role for this molecule in T-cell-mediated cytotoxicity.
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PMID:Membrane form of TNF alpha induces both cell lysis and apoptosis in susceptible target cells. 866 Aug 44

During acute inflammation, P-selectin is transiently mobilized from Weibel-Palade bodies to the surface of histamine-activated endothelial cells, where it mediates rolling adhesion of neutrophils under hydrodynamic flow. During chronic or allergic inflammation, sustained expression of P-selectin on the endothelial cell surface has been observed. We found that the cytokines interleukin 4 (IL-4) or oncostatin M (OSM) induced a five- to ninefold increase in P-selectin messenger RNA (mRNA) in human umbilical vein endothelial cells (HUVEC) that persisted as long as 72 h. IL-4 elevated P-selectin mRNA by increasing its transcription rate rather than by prolonging its already long half-life. Stimulation of P-selectin transcription by IL-4 or OSM required new protein synthesis and tyrosine phosphorylation of cellular proteins. Tumor necrosis factor alpha, IL-1 beta, lipopolysaccharide, or IL-3 did not increase P-selectin mRNA in HUVEC, and did not augment the IL-4-induced increase in P-selectin transcripts. IL-4 or OSM increased P-selectin protein on the cell surface as well as in Weibel-Palade bodies. Under flow conditions, neutrophils rolled on P-selectin expressed by IL-4-treated HUVEC, and even more neutrophils rolled on P-selectin after IL-4-treated HUVEC were stimulated with histamine. These data demonstrate that IL-4 or OSM stimulates endothelial cells to synthesize more P-selectin over prolonged periods. The increased expression of P-selectin may facilitate the emigration of leukocytes into sites of chronic or allergic inflammation.
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PMID:Interleukin 4 or oncostatin M induces a prolonged increase in P-selectin mRNA and protein in human endothelial cells. 869 Nov 52

Tumor necrosis factor alpha (TNF alpha) was repeatedly microinfused into the lateral ventricle of guinea pig brains at a dose of 200 ng, 4 times within 150 min, at intervals of 3 days. In comparison to guinea pigs infused with solvent according to the same time schedule. the animals responded to TNF alpha with pronounced fevers. The quantity of the fever response was the same after each of the 4 microinfusions of TNF alpha. Three days after the last infusion of TNF alpha or solvent all animals received an intramuscular injection of bacterial lipopolysaccharide (LPS). The fever in response to LPS was the same in both groups. Thus, the reported development of tolerance to repeated systemic administration of TNF alpha 1-3 does not develop inside the blood-brain barrier. Also, the febrile response to LPS is not influenced by repeated central pre-treatment with TNF alpha, whereas repeated peripheral treatment does have an effect.
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PMID:Lack of tolerance development to tumor necrosis factor alpha inside the central nervous system. 877 47


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