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)

Bacterial lipopolysaccharide (LPS) induces a strong B-cell proliferative response with subsequent differentiation, through a complex signal transduction pathway. This process is known to be mediated through protein kinase C (PKC) translocation without Ca2+ mobilization. Here, we show that B-cell proliferative responses induced by five different LPS preparations, as well as by F(ab')2 anti-IgM antibodies, are inhibited by the tyrosine kinase inhibitors, genistein and herbimycin A. In contrast, B-cell proliferation induced by the combination of phorbol 12-myristate 13-acetate (PMA) plus ionomycin was not influenced by treatment with either herbimycin A or genistein. These data indicate that tyrosine phosphorylation is required to initiate B-cell proliferation by LPS.
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PMID:Requirement for tyrosine phosphorylation in lipopolysaccharide-induced murine B-cell proliferation. 830 17

It is believed that induction of cytokine expression by bacterial cell wall components plays a role in the development and course of sepsis. However, most attention has been focused on lipopolysaccharide (LPS). We studied the ability of N-acetylglucosaminyl-1,6-anhydro-N-acetylmuramyl-L-alanyl-D- isoglutamyl-m-diaminopimelyl-D-alanine (G(Anh)MTetra), a naturally occurring breakdown product of peptidoglycan that is produced by soluble lytic transglycosylase of Escherichia coli, to induce cytokine expression in human monocytes. G(Anh)MTetra was found to strongly induce interleukin (IL)-1 beta and IL-6 mRNA expression after 2 h and IL-1 beta and IL-6 protein secretion after 48 h of activation. The increase in mRNA accumulation was at least partly due to an increase in the transcription rates of the respective genes and was accompanied by a strong induction of nuclear factor-kappa B and activator protein-1 transcription factor expression. Experiments using inhibitors of protein kinase C, protein kinase A, and tyrosine kinase-dependent pathways revealed that G(Anh)MTetra-induced IL-1 beta and IL-6 mRNA expression involves activation of an H7-inhibitable pathway. By using the protein synthesis inhibitor cycloheximide, it was shown that G(Anh)MTetra-induced IL-6 mRNA expression depends on the synthesis of new protein, whereas G(Anh)MTetra-induced IL-1 beta mRNA accumulation does not. When responses to G(Anh)MTetra were compared with those to LPS and muramyldipeptide (MDP), it was found that the optimal response to G(Anh)MTetra induction was similar to that of LPS but significantly higher than the response to MDP. Furthermore, maximal G(Anh)MTetra-induced IL-1 beta and IL-6 mRNA expression could be enhanced by co-stimulation with LPS or MDP, suggesting that different receptors and/or transduction pathways were involved. These results indicate that G(Anh)MTetra induces IL-1 beta and IL-6 expression in human monocytes suggesting a possible role for G(Anh)MTetra in the release of cytokines during sepsis.
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PMID:G(Anh)MTetra, a natural bacterial cell wall breakdown product, induces interleukin-1 beta and interleukin-6 expression in human monocytes. A study of the molecular mechanisms involved in inflammatory cytokine expression. 830 82

Resting murine B lymphocytes can be induced to proliferate by cross-linking membrane immunoglobulin, the antigen receptor, or by contact with activated helper T lymphocytes in the absence of a signal through membrane immunoglobulin. Little is known about the molecular nature of contact-dependent T cell help. To determine whether helper T cells activate B cells through different signal transduction and second messenger pathways from those used by membrane immunoglobulin, the effects of drugs which block activation of B cells through membrane immunoglobulin were measured on B cell activation by contact with anti-CD3-activated and fixed T helper cells. Cyclosporin A, phorbol esters added at the time of activation, and cAMP agonists all block activation of B cells through membrane immunoglobulin at concentrations at least 100-fold lower than those necessary to block B cell activation by contact with activated Th1 or Th2 helper T cells. Depletion of protein kinase C by pretreatment of B cells with phorbol ester inhibits the proliferative response to anti-immunoglobulin but not the response to contact with activated T cells. The B cell response to lipopolysaccharide is intermediate in sensitivity to cyclosporin A and cAMP agonists, and resembles the response to activated T cells in resistance to phorbol esters and protein kinase C depletion. Various protein kinase inhibitors did not distinguish among these B cell activation pathways, except for the tyrosine kinase inhibitor, herbimycin A, which inhibited anti-immunoglobulin responses at 3- to 5-fold lower concentrations.
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PMID:Antigen and helper T lymphocytes activate B lymphocytes by distinct signaling pathways. 841 91

Engagement of many cell surface receptors results in tyrosine phosphorylation of an overlapping set of protein substrates. Some proteins, such as the adaptor protein Shc, and a frequently observed Shc-associated protein, p145, are common substrates in a variety of receptor signaling pathways and are thus of special interest. Tyrosine-phosphorylated Shc and p145 coprecipitated with anti-Shc antibodies following B cell antigen receptor (BCR) cross-linking or interleukin-4 (IL-4) receptor activation in B cells, and after lipopolysaccharide (LPS) treatment or IgG Fc receptor (Fc gamma R) cross-linking in macrophages. In the case of BCR stimulation, we have shown that this represented the formation of an inducible complex. Furthermore, in response to LPS activation or Fc gamma R cross-linking of macrophages and BCR cross-linking (but not IL-4 treatment) of B cells, we observed a similar tyrosine-phosphorylated p145 protein associated with the tyrosine kinase Syk. We did not detect any Shc associated with Syk, indicating that a trimolecular complex of Shc, Syk, and p145 was not formed in significant amounts. By several criteria, the Syk-associated p145 was very likely the same protein as the previously identified Shc-associated p145. The Syk-associated p145 and the Shc-associated p145 exhibited identical mobility by SDS-polyacrylamide gel electrophoresis and identical patterns of induced tyrosine phosphorylation. The p145 protein that coprecipitated with either Shc or Syk bound to a GST-Shc fusion protein. In addition, a monoclonal antibody developed against Shc-associated p145 also immunoblotted the Syk-associated p145. The observations that p145 associated with both Shc and Syk proteins, in response to stimulation of a variety of receptors, suggest that it plays an important role in coordinating early signaling events.
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PMID:Activation-induced association of a 145-kDa tyrosine-phosphorylated protein with Shc and Syk in B lymphocytes and macrophages. 855 43

We designed a microplate-based assay method for mitogen-activated protein (MAP) kinase. Using anion-exchanger resin, MAP kinases from murine macrophages were partially purified in 96-well plates. The activities of these purified enzymes correlated well with those detected in heretofore used assays. The micro-trap phosphorylation assay has advantages over conventional methods (immunoprecipitation, Western blotting for the detection of mobility shift, or kinase detection assay in myelin basic protein (MBP)-containing gel), in terms of sensitivity, economy and rapid execution for hundreds of samples. Using micro-trap phosphorylation assay, it was demonstrated that MAP kinase activities in macrophages were persistently increased by lipopolysaccharide (LPS) stimulation, and this activation was inhibited by polymyxin B or tyrosine kinase inhibitors. This method is expected to give a wide range of application, such as determining effects of drug inhibitors or antisense oligonucleotides on MAP kinases, or measuring the various protein kinases after specificity controls were done.
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PMID:Micro-trap phosphorylation assay of mitogen-activated protein (MAP) kinases to detect their activation by lipopolysaccharides. 860 13

Activation of macrophages by bacterial lipopolysaccharide (LPS) induces transcription of genes that encode for proinflammatory regulators of the immune response. Previous work has suggested that activation of the transcription factor activator protein 1 (AP-1) is one LPS-induced event that mediates this response. Consistent with this notion, we found that LPS stimulated AP-1-mediated transcription of a transfected reporter gene in the murine macrophage cell line RAW 264.7. As AP-1 activity is regulated in part by activation of the c-Jun N-terminal kinase (JNK), which phosphorylates and subsequently increases the transcriptional activity of c-Jun, we examined whether LPS treatment of macrophages resulted in activation of this kinase. LPS treatment of RAW 264.7 cells, murine bone marrow-derived macrophages, and the human monocyte cell line THP-1 resulted in rapid activation of the p46 and p54 isoforms of JNK. Treatment with wild-type and rough mutant forms of LPS and synthetic lipid A resulted in JNK activation, while pretreatment with the tyrosine kinase inhibitor herbimycin A inhibited this response. Binding of LPS-LPS binding protein (LBP) complexes to CD14, a surface receptor that mediates many LPS responses, was found to be crucial, as pretreatment of THP-1 cells with the monoclonal antibody 60b, which blocks this binding, inhibited JNK activation. These results suggest that LPS activation of JNK in monocyte/macrophage cells is a CD14- and protein tyrosine phosphorylation-dependent event that may mediate the early activation of AP-1 in regulating LPS-triggered gene induction.
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PMID:Activation of c-Jun N-terminal kinase in bacterial lipopolysaccharide-stimulated macrophages. 861 Jan 16

Human vascular endothelial cells (HUVECs), which do not display the lipopolysaccharide (LPS) receptor CD14, were examined for protein tyrosine phosphorylation after LPS stimulation in the presence and absence of soluble CD14 (sCD14). By phosphotyrosine Western blotting and immunocomplex kinase assays we show that LPS was capable of inducing in these cells rapid protein tyrosine phosphorylation and kinase activation of two members of the mitogen-activated protein kinase (MAPK) family erk-1 and the newly discovered p38, requiring the presence of sCD14. LPS-induced tyrosine phosphorylation of MAPK was associated with increased transcript- and surface protein expression of intracellular adhesion molecule-1 by HUVECs. MAPK phosphorylation and activation was induced by LPS in concentrations as little as 30 ng/mL and as early as 15 minutes after stimulation. Furthermore, tyrosine kinase inhibitors such as Genistein partially inhibited this effect. These results show that LPS triggers similar signaling events in both CD14+ myelo-monocytic cells and cells lacking the putative LPS-receptor CD14, suggesting the presence of a common, yet unidentified element in LPS-signaling in both cell types.
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PMID:Lipopolysaccharide induces the rapid tyrosine phosphorylation of the mitogen-activated protein kinases erk-1 and p38 in cultured human vascular endothelial cells requiring the presence of soluble CD14. 863 98

Tumour necrosis factor-alpha (TNF-alpha), an important mediator in both immune and inflammation responses, is one of the major cytokines released by activated macrophages. The present study shows that, during macrophage activation, protein tyrosine phosphorylation of STAT1 alpha and ERK2 occurred as an immediate early signal, whereas maximum TNF-alpha mRNA transcription appeared at 3 hr, precursor TNF-alpha formation at 3 to 4 hr, and TNF-alpha release at 5 to 6 hr after stimulation of an RPMI-1640-based induction medium containing lipopolysaccharide (100 ng/ml), interferon-gamma (100 U/ml), and 0.5% bovine serum albumin. Herbimycin A, a tyrosine kinase inhibitor, suppresses protein tyrosine phosphorylation of STAT1 alpha and ERK2 and also blocks TNF-alpha production by resident peritoneal macrophages from BALB/c mice, suggesting a possible association between protein tyrosine phosphorylation of STAT1 alpha and ERK2 and macrophage activation resulting in TNF-alpha production.
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PMID:Dynamic production of tumour necrosis factor-alpha (TNF-alpha) messenger RNA, intracellular and extracellular TNF-alpha by murine macrophages and possible association with protein tyrosine phosphorylation of STAT1 alpha and ERK2 as an early signal. 867 7

In human monocytes, interleukin 1beta protein production and steady state mRNA levels are increased in response to lipopolysaccharide, predominantly as a result of increased transcription of the interleukin 1beta gene. Expression of interleukin 1beta and other cytokines, such as interleukin 6 and tumor necrosis factor alpha, has been shown to be dependent on the activation of the transcription factor, NFkappaB. Since recent studies have shown that lipopolysaccharide-induced tyrosine kinase activation is not required for NFkappaB nuclear translocation, we sought to determine whether NFkappaB translocated in the absence of tyrosine kinase activity was active in stimulating transcription. We have found that, in the human pro-monocytic cell line, THP-1, the lipopolysaccharide-induced expression of interleukin 1beta is dependent on tyrosine kinase activation. Tyrosine kinases are not required for lipopolysaccharide-mediated nuclear translocation of NFkappaB. However, in the absence of tyrosine kinase activity, the ability of NFkappaB to stimulate transcription is impaired. This inhibition of transcription is specific for NFkappaB; in the absence of tyrosine kinase activity, AP-1-dependent transcription is enhanced. These results suggest that, while lipopolysaccharide-induced expression of inflammatory mediators requires tyrosine kinase activity, tyrosine kinase activity is not obligatory for lipopolysaccharide signal transduction.
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PMID:Protein-tyrosine kinase activation is required for lipopolysaccharide induction of interleukin 1beta and NFkappaB activation, but not NFkappaB nuclear translocation. 870 66

Endotoxin, known as lipopolysaccharide (LPS), is a component of gram-negative bacterial cell walls and is a potent immunostimulator, inducing the release of several cytokines, such as tumor necrosis factor alpha (TNF alpha) and interleukins (IL) 1, 6, and 8. A previous study with immature rats revealed that exogenous administration of LPS inhibits ovarian estradiol secretion in response to eCG. The present study was undertaken in order to determine whether LPS could directly inhibit rat granulosa cell (GC) steroid secretion. GC were collected and purified from 26-day-old hypophysectomized female rats (hypophysectomy on Day 23). Purified GC were highly responsive to FSH (1-100 ng/ml), leading to increased estradiol, progesterone, and cAMP accumulation in culture media. GC were also capable of binding 125I-labeled hCG and were responsive to LH stimulation. Treatment of GC with LPS (1-100 ng/ml) led to a significant (p < 0.01) dose-dependent decrease in LH-stimulated estradiol accumulation in culture media (maximum 75% inhibition). However, treatment of GC with LPS had no significant effect on FSH-stimulated progesterone or estradiol, or LH-stimulated progesterone accumulation in culture media. GC stimulated with 8-bromo cAMP were also insensitive to the effects of LPS. LPS had no significant effect on 125I-labeled hCG binding to GC homogenates, nor did it have any significant effect on FSH or LH-stimulated cAMP accumulation. Treatment of both FSH and LH-stimulated GC with LPS was associated with an increase in IL-6 bioactivity in culture media. This effect could be blocked with the nonreceptor tyrosine kinase inhibitor herbimycin A. TNF alpha bioactivity was undetectable with or without LPS challenge. Direct challenge of GC with recombinant murine IL-6 had no effect on either FSH or LH-stimulated estradiol whereas TNF alpha inhibited FSH-stimulated estradiol secretion. Collectively, these results suggest that the inhibitory effects of LPS were not mediated by either IL-6 or TNF alpha. Treatment of GC with the epidermal growth factor receptor tyrosine kinase inhibitor, tyrphostin A46, blocked the inhibitory effects of LPS on steroid secretion and was associated with an increased cAMP accumulation in culture media. The results indicate that LPS inhibits in vitro GC estradiol secretion. This effect appears to be restricted to the LH-stimulated aromatization of androgens to estrogen and may involve a tyrosine kinase signaling pathway.
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PMID:Lipopolysaccharide inhibits in vitro luteinizing hormone-stimulated rat ovarian granulosa cell estradiol but not progesterone secretion. 872 69


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