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

Our results suggest that CKs, in particular Interleukin-1 and Tumor Necrosis Factor (TNF)-alpha, are involved in the pathogenesis of some neurological disorders and HIV infection. Infact, we observed an exaggerated spontaneous release of TNF-alpha in patients with migraine without aura. Furthermore, in a broad spectrum of patients with HIV-infection we have also found increased amounts of serum TNF-alfa and IL-1. Interestingly, a strict correlation between plasma lipopolysaccharide (LPS) and IL-1 or TNF-alpha levels seems to exist in both group of patients, thus indicating that LPS could account for the production of CKs in the course of the above diseases.
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PMID:Neurological damage mediated by cytokines. 141 60

Continuous lipopolysaccharide (LPS) infusion in pigs induced death in approximately half of the animals and a prolonged state of shock (up to 3 hours of experimental observation period, i.e., two hours after discontinuation of LPS infusion) in the surviving animals. Lethal-induced shock was marked by huge release of Tumor Necrosis Factor (TNF) into the blood, whereas eicosanoid and Platelet Activating Factor (PAF) levels remained unchanged. In pigs surviving LPS-infusion but still remaining in a state of shock, transient increases in PAF and thromboxane levels were observed, whereas prostacyclin and leukotrienes values remained above normal levels up to the end of the observation period. It is concluded that different types of mediators play a role in LPS-induced lethal shock as compared to non-lethal prolonged state of shock.
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PMID:Lethal and non-lethal course of endotoxic shock is determined by interactions between tumor necrosis factor, platelet activating factor and eicosanoids. 148 41

Cellular mechanisms and environmental factors contributing to wound failure following shock and wound contamination are unclear. The activation of macrophages by exposure to hypoxia (pO2 less than 20) and/or lipopolysaccharide (10 micrograms/ml) in vitro was investigated for its effect on macrophage regulation of fibroblast proliferation. The effect on fibroblast proliferation of conditioned medium from activated murine macrophages or co-culture with activated macrophages was tested by measuring 3T3 fibroblast incorporation of 3H-thymidine and culture DNA content. Unstimulated macrophages produced growth factors that increase fibroblast proliferation (proliferation index (PI) = 1.4 +/- 0.15, p less than 0.05 vs. control). Activation by hypoxia alone had little effect on macrophage regulation of fibroplasia (PI = 1.55 +/- 0.28, N.S. vs. unstimulated macrophages). LPS activated macrophages suppressed fibroplasia and the combination of hypoxia with LPS augmented the suppression (PI = 0.5 +/- 0.11, LPS alone, p less than 0.05 and 0.25 +/- 0.05, LPS + hypoxia, p less than 0.01). In addition, hypoxia + LPS treated co-cultures had reduced DNA contents, suggesting reduced cell numbers (12.5 +/- 2.6 micrograms vs. 8.2 +/- 2.0 micrograms). We screened several macrophage cytokines for their direct effect on 3T3 proliferation and found that mr-Tumor Necrosis Factor-alpha (150 units) also suppressed proliferation. Conditioned supernatants from LPS activated macrophages contained 12 +/- 2 units of mrTNF as measured by L929 cytolysis; however, this was significantly less than required to induce suppression of proliferation by direct addition. The regulatory role of the macrophage appears to be dependent on its level of activation. Activation by hypoxia and LPS altered macrophage regulation of fibroblast proliferation from stimulation to suppression.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hypoxia and endotoxin induce macrophage-mediated suppression of fibroblast proliferation. 266 3

Tumor Necrosis Factor (TNF) is an active component of serum taken from Corynebacterium parvum (C. parvum) infected mice treated with lipopolysaccharide (LPS). To locate the production site of TNF, we tried to block TNF production by using the following reagents; carrageenan, hydrocortisone, and trypan blue. Following the injection of a large dose of carrageenan, administered before C. parvum treatment, TNF production was completely blocked. However, when administered after C. parvum treatment but prior to LPS injection, no blockage was observed. Injecting hydrocortisone before the LPS injection also blocked TNF release. However, this treatment, when administered before the injection of C. parvum, had no observable influence on TNF production. A large dose of trypan blue, administered before the LPS injection, also blocked the release of TNF. A low dose of trypan blue resulted in only partial blockage of TNF production. A large dose of trypan blue, administered prior to C. parvum treatment, also showed partial blockage of TNF production. Macrophage-enriched peritoneal exudate cells (PEC), taken from mice infected with C. parvum, released TNF into the supernatant after stimulation with LPS. These results strongly suggest that the production site of TNF is located within the activated macrophage and deeply related with lysosome.
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PMID:Research on the production site of tumor necrosis factor (TNF). 733 69

When administered to patients, various biotechnology products may induce early toxic effects mediated by a cytokine cascade in which Tumor Necrosis Factor-alpha (TNF-alpha) plays a central role. The mechanisms of these toxic reactions have been extensively documented in the clinical model of the CD3 monoclonal antibody (mAb), OKT3. In order to develop a preclinical test for assessing the potential of mAbs or recombinant molecules to induce acute reactions when administered to patients, we investigated different in vitro culture systems for TNF-alpha secretion, using human blood cells. OKT3 and bacterial lipopolysaccharide (LPS) were used as positive controls. By comparing different culture conditions and kinetics, we concluded that 6-h supernatants of plasma-depleted whole blood contained high amounts of TNF-alpha in cultures stimulated by OKT3 or LPS, but not in those performed in the absence of exogenous stimulant or in the presence of mAbs which do not induce toxic reactions in vivo. This in vitro assay may be applied to the preclinical evaluation of the risk of cytokine-mediated toxicity in vivo. Owing to its simplicity, it could be used for preclinical investigation of inter-individual differences in the susceptibility to 'activation syndrome'.
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PMID:TNF-alpha production as an in vitro assay predictive of cytokine-mediated toxic reactions induced by monoclonal antibodies. 762 79

Polymorphs (PMN) and monocytes/macrophages (Mo) play a very important role in the host defence since they participate to inflammatory processes, tissue repairing and antitumor activity. Previous studies showed that lipopolysaccharide (LPS)-activated Mo are able to upregulate PMN phagocytic ability via cell-to-cell contact mechanisms mediated by bound to Mo membrane (m) cytokines (CKs), such as Tumor Necrosis Factor (TNF)-alpha, Interleukin (IL)-1 alpha and IL-1 beta. Based on these grounds, the role of Mo m-associated IL-6 and IL-8 on the modulation of PMN activity has been evaluated. In the first step, PMN incubated with lipid A (LA)-activated Mo showed an increased phagocytosis dependent on cell-to-cell contact only. In the second step, LA-activated Mo were pretreated with antirecombinant human (Rhu) IL-6 and IL-8 monoclonal antibodies (MoAbs), respectively and, in such a way, the enhanced phagocytic activity of PMN was abrogated. In the third step, PMN incubated with LA-activated supernatants (AS) from PBMC cultures exhibited an enhanced phagocytic activity, that was abrogated when LA-AS were pretreated with anti-Rhu IL-6 and anti-Rhu IL-8 MoAbs, respectively. These data suggest that IL-6 and IL-8 associated to Mo membrane may modulate PMN activation through a cell-to-cell contact dependent pathway.
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PMID:Enhancement of polymorphonuclear cell phagocytosis by lipid A-activated monocytes via cell-to-cell contact: a possible role for membrane-associated interleukin-6 and interleukin-8. 775 74

A model for the coculture of chondrocytes in gelified agarose with mononuclear cells was developed to serve as an in vitro equivalent for cytokine-mediated events at the cartilage-synovial pannus junction in destructive arthropathies. Chondrocytes cultured in agarose keep their phenotypic stability. They release cartilage-specific aggrecans into the surrounding artificial matrix. When activated with lipopolysaccharide for 1 h, mononuclear cells release Interleukin 1 beta and Tumor Necrosis Factor alpha, thereby stimulating the chondrocytes to produce Interleukin 6, to diminish incorporation of 35S into aggrecans, and to degrade these intercellular macromolecules. This coculture model is a useful tool for studying interactions between inflammatory cells and target cells. To demonstrate its usefulness, the effect of three anti-inflammatory drugs (piroxicam, sulphasalazine, and hydrocortisone) on cytokine release by mononuclear cells, and subsequently on chondrocyte aggrecan metabolism was studied. The drugs were unable to abrogate Interleukin 1 and Tumor Necrosis Factor alpha release by activated mononuclear cells. Therefore, these pharmacological agents did not protect the artificial target tissue against cytokine-mediated degradation.
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PMID:Coculture of human articular chondrocytes with peripheral blood mononuclear cells as a model to study cytokine-mediated interactions between inflammatory cells and target cells in the rheumatoid joint. 788 28

Survival after lipopolysaccharide challenge (LD80, 20 mg.kg-1, i.p.) was significantly enhanced by previous treatment with a microdose of LPS (50 micrograms.kg-1, i.v.). When NG-monomethyl-L-arginine, a specific inhibitor of the formation of nitric oxide from L-arginine, was given 30 minutes before microdose, survival was significantly reduced. When we monitored the serum Tumor Necrosis Factor (TNF) levels in both groups a significant reduction of TNF level after the microdose was observed in mice previously treated with L-NMMA. The ability of L-NNMA to reduce TNF release was dose dependent.
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PMID:Role of nitric oxide pathway in the protection against lethal endotoxemia afforded by low doses of lipopolysaccharide. 846 Oct 2

Tumor Necrosis Factor alpha (TNF alpha) is a cytokine mediator that is produced primarily by activated monocytes/macrophages in response to endotoxin/lipopolysaccharide (LPS) as well as other stimuli. The second messenger systems that regulate the synthesis and release of TNF alpha are not clearly defined. In the present study, the role of protein kinase C (PKC) in the production of TNF alpha was investigated in human peripheral blood monocytes stimulated with either LPS or zymosan. Two broad spectrum protein kinase inhibitors (staurosporine and K252a) and two PKC specific inhibitors (calphostin C and chelerythrine), were used as probes to delineate the involvement of PKC in the production of TNF alpha. The results indicate that inhibition of PKC diminished LPS- or zymosan- induced TNF alpha production in a concentration-dependent manner. The IC50 values for the inhibition of TNF alpha production were 0.2 nM for staurosporine, and 20 nM for K252a, Calphostin C and chelerythrine. Furthermore, long term PMA treatment of these cells (to abrogate PKC-mediated responses) resulted in a significant reduction of stimuli-induced TNF alpha production. LPS and zymosan also induced an increase in membrane associated PKC activity in human monocytes, which could be inhibited by pretreatment of the cells with calphostin C. Finally, western blot analysis with PKC isoform-specific antibodies demonstrates that the alpha and xi are the predominent isoforms expressed in human monocytes. These data strongly suggest that an initial step in TNF alpha production by human monocytes challenged with physiological stimulants, such as LPS and zymosan, involves a PKC-dependent mechanism.
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PMID:Protein kinase C regulates TNF-alpha production by human monocytes. 849 Jan 3

TWEAK is a newly identified member of the Tumor Necrosis Factor (TNF) family of proteins which are involved in many immunoinflammatory mechanisms. The putative role of TWEAK in inflammation was analyzed in mice treated with lipopolysaccharide (LPS), a strong inducer of the immuno-inflammatory responses. TWEAK mRNA rapidly disappeared in all the tissues tested. Analysis of LPS-treated thioglycolate-elicited peritoneal macrophages revealed that the rapid loss of TWEAK mRNA was due to its active destabilization. In chronic pathologies like autoimmune hemolytic anemia in the NZB mouse strain or systemic lupus erythematosus (SLE) in the BXSB mouse strain, TWEAK mRNA was shown to be reduced concomitantly to the development of chronic autoimmune diseases. These results demonstrated that TWEAK mRNA, contrary to TNF mRNA, is stable, ubiquitously distributed in tissues, and is down-regulated after LPS treatment or in chronic inflammation, suggesting that TWEAK could be an important factor, along with TNF, in acute and chronic inflammations.
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PMID:Down-regulated expression of TWEAK mRNA in acute and chronic inflammatory pathologies. 1111 33


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