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)

Previous studies have shown that macrophages play an important role in both the initiation of protective responses and the effector mechanism of immunity to Toxoplasma gondii. The purpose of this investigation was to characterize the responses of macrophages to a soluble antigen extract of T. gondii tachyzoites (STAg) in comparison with a prototypic macrophage-activating agent, lipopolysaccharide (LPS), and to determine whether STAg-induced signaling requires a functional Lps gene. Toward this end, tumor necrosis factor (TNF) secretion, a panel of six LPS-inducible genes, and protein tyrosine phosphorylation were examined to gain insights into macrophage responses to STAg. STAg stimulated both C3H/OuJ (Lpsn) and C3H/HeJ (Lpsd) macrophages to secrete bioactive TNF-alpha and to express a subset of LPS-inducible genes (encoding TNF-alpha, TNF receptor 2, and interleukin-1 beta). In contrast to LPS, STAg failed to stimulate Lpsn or Lpsd macrophages to express genes encoding IP-10, D3, or D8. STAg also induced a pattern of tyrosine phosphorylation identical to that induced by LPS; mitogen-activated protein kinase 47-kDa and 43-kDa isoforms and a 41-kDa protein of undetermined identity were inducibly phosphorylated. The ability of STAg to induce TNF-alpha, encoded by a subset of LPS-inducible genes, and tyrosine phosphoproteins was not affected by LPS inhibitors, confirming that the macrophage response to the parasite extract could not be attributed to LPS contamination. We propose that STAg, while differing from LPS in the pattern of macrophage genes induced, may share with LPS two signaling pathways that are intact in Lpsd macrophages.
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PMID:Toxoplasma gondii soluble antigen induces a subset of lipopolysaccharide-inducible genes and tyrosine phosphoproteins in peritoneal macrophages. 803 14

Previous studies demonstrated that the intraperitoneal injection of epidermal growth factor (EGF) into mice resulted in the appearance, within minutes, of several tyrosine-phosphorylated proteins in liver nuclei. Two of these proteins have been identified as the transcription factors p91/p84 (Stat1 alpha/1 beta) (Ruff-Jamison, S., Chen, K., and Cohen, S. (1993) Science 261, 1733-1736). We have now identified, by Western blotting and immunoprecipitation, an additional EGF-modulated transcription factor, Stat3. We find that Stat3 is tyrosine-phosphorylated and present in mouse liver nuclei following either EGF or lipopolysaccharide administration. Gel shift analyses show that Stat3 is capable of specifically binding the SIE (a DNA sequence present in the c-fos promoter). Three active SIE binding complexes (SIF A, B, and C) exist in the nucleus after the administration of EGF: one complex that contains Stat3, one that contains Stat1, and a third complex that appears to contain both proteins. Only one active SIE binding complex, containing Stat3, was detected after the administration of lipopolysaccharide.
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PMID:Epidermal growth factor and lipopolysaccharide activate Stat3 transcription factor in mouse liver. 807 11

The monoclonal antibody YsT9.1 is specific for the lipopolysaccharide A antigen of Brucella abortus. A complex formed between the Fab of YsT9.1 (Ab1) and the Fab of its antidiotopic monoclonal antibody T91AJ5 (Ab2) has been crystallized, and data have been collected to 2.8 A resolution. The space group is monoclinic P2(1), with one molecule per asymmetric unit. The structure was solved using a limited Patterson-correlation search over the asymmetric-unit of rotation space, and has been refined to an R-factor of 0.174. The complex is a head-to-head dimer, with the contact between the two Fabs almost completely restricted to their hypervariable loops. The interactions between the two Fabs in the complex are dominated by tyrosine residues, not only in the formation of hydrogen bonds, but in their participation in an aromatic ring network that spans the two Fv domains. The anti-idiotope was found to be unable to carry an internal image of the antigen and induce polysaccharide-specific "anti-anti-idiotopes" (Ab3) because the polysaccharide binding cleft on the Ab1 is too narrow and deep to allow comprehensive contact with the binding site of Ab2. The antibody T91AJ5 therefore is a class gamma anti-idiotope. The contact surfaces of the two Fabs are highly complementary; however, they are distinctly different in character. Each Fab has two separate binding surfaces of approximately equal size, but while the two binding surfaces of Ab1 are partitioned between the light and heavy chains, the two binding surfaces of Ab2 are shared between the chains, with the heavy chain responsible for about 60% of the total binding area. The structure of the unliganded Fab of Ab2 has also been solved by molecular replacement, and refined to an R-factor of 0.152 at 2.8 A resolution. This Fab crystallizes in the orthorhombic space group P2(1)2(1)2(1), with one molecule per asymmetric unit. The second hypervariable loop of the heavy chain of the Ab2 Fab is observed to undergo a significant and necessary conformational rearrangement in going from the unliganded to complexed form, and thus complex formation is an example of "induced fit" of antigen to antibody. The unliganded Ab1 Fab packs in the standard head-to-tail fashion observed for other Fabs. This mode of packing is precluded in the complex, by its head-to-head nature, and it is found to pack in tilted layers with most intermolecular contacts made between adjacent Ab2 Fab molecules.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Exploring the mimicry of polysaccharide antigens by anti-idiotypic antibodies. The crystallization, molecular replacement, and refinement to 2.8 A resolution of an idiotope-anti-idiotope Fab complex and of the unliganded anti-idiotope Fab. 807 93

Activation of monocytes by bacterial lipopolysaccharides (LPSs) is a central component in the pathogenesis of septic shock syndrome. Interleukin 10 (IL-10) is a potent monocyte-deactivating factor and transcriptionally inhibits LPS-induced expression of proinflammatory mediators. The intracellular signaling pathways of LPS have been only partially characterized and mechanisms of IL-10 signaling remain unknown. We show that LPS activates the protein tyrosine kinase (PTK) p56lyn and that this is associated with tyrosine phosphorylation of the protooncogene product Vav. These events are completely blocked by the tyrosine kinase inhibitor herbimycin A. LPS also increases Ras activation in monocytes. LPS-triggered phosphorylation of mitogen-activated protein kinase is a downstream activation event that is also reduced by herbimycin A. Analysis of the IL-10 effects shows that it completely inhibits the p56lyn tyrosine kinase activation and all other subsequent events in this pathway including Ras activation. The IL-10 effects are selective since it reduced PTK-dependent cytokine mRNA expression but not the PTK independent induction of c-jun and c-fos mRNA in LPS-activated monocytes. These results identify the Ras signaling pathway as a component of intracellular signaling in LPS-stimulated monocytes and define early events in this response as targets of monocyte deactivation by IL-10.
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PMID:Monocyte deactivation by interleukin 10 via inhibition of tyrosine kinase activity and the Ras signaling pathway. 807 29

This study demonstrates for the first time that teleost, specifically channel catfish, B cells proliferate in response to membrane immunoglobulin (mIgM) cross-linking. An early activation event mediated by anti-IgM ligation involved a rapid increase in intracellular calcium levels similar to the situation seen in mammalian B cells. In addition, catfish B cells, like mammalian B cells, did not exhibit such calcium changes following stimulation with lipopolysaccharide. Another consequence of catfish B cell mIgM cross linking was the rapid induction of intracellular protein phosphorylation. A number of proteins were phosphorylated on tyrosine residues within minutes after anti-Ig stimulation, indicating the activation of protein tyrosine kinases similar to the situation observed in mammalian B cells. These early intracellular activation events suggest that fish B cells, like mammalian B cells, employ a conserved signal transduction system upon mIgM ligation. This ability to transduce activation signals, coupled with the fact that catfish mIgM have a very short cytoplasmic tail, implies that catfish mIgM is probably associated with accessory molecules required for signal transduction. In this regard, several of the tyrosine phosphorylated catfish proteins exhibited relative molecular weights similar to the mammalian Ig-alpha and Ig-beta/gamma accessory molecules, and may represent candidates for the putative catfish mIgM accessory molecules.
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PMID:Activation of channel catfish B cells by membrane immunoglobulin cross-linking. 808 19

Taxol is the prototype of a new class of microtubule stabilizing agents with promising anticancer activity. Several studies show that taxol mimics the actions of lipopolysaccharide (LPS) on murine macrophages. To investigate the mechanism of taxol-induced macrophage stimulation, we evaluated the ability of Rhodobacter sphaeroides diphosphoryl lipid A (RsDPLA) and SDZ 880.431 to block taxol-induced effects. RsDPLA and SDZ 880.431 are lipid A analogues that lack LPS-like activity, but inhibit the actions of LPS, presumably by blocking critical cellular binding sites. We report that RsDPLA and SDZ 880.431 potently inhibited taxol-induced TNF secretion, gene activation, and protein-tyrosine phosphorylation. The role of microtubules in taxol signaling was investigated. Taxol-induced microtubule bundling in primary and transformed RAW 264.7 macrophages was not blocked by RsDPLA or SDZ 880.431. Taxotere, a semisynthetic taxoid, was more potent than taxol as an inducer of microtubule bundling, but did not induce tumor necrosis factor alpha secretion and gene activation. These data dissociate the microtubule effects of taxol from macrophage stimulation and suggest that taxol stimulates macrophages through an LPS receptor-dependent mechanism. The results underscore the potential of taxol as a tool for studying LPS receptor activation and provide insights into possible therapeutic actions of this new class of drugs.
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PMID:Lipopolysaccharide antagonists block taxol-induced signaling in murine macrophages. 810 63

Antipyretic properties have been ascribed to arginine vasopressin (AVP), and the site where its antipyretic effects are mediated in the brain was identified as the ventrolateral septum of the limbic system. In guinea pigs, the majority of AVP projections to the septum originate from parvocellular neurons of the hypothalamic paraventricular nucleus (PVN). Electrical stimulation of the PVN with 10-s trains of current pulses (duration 1 ms, frequency 20 Hz, amplitude 8 V, current 0.205 +/- 0.017 mA) reduced the febrile response to an intramuscular injection of 20 micrograms/kg lipopolysaccharide (LPS from Escherichia coli, 0111: B4) by 54% compared with unstimulated animals. This reduction in fever by electrical PVN stimulation was partly reversed by a simultaneous intraseptal microinfusion of the vasopressinergic V1-receptor antagonist d(CH2)5[Tyr(Met)2]AVP at a concentration of 10(-5) mol for 6 h with an infusion speed of 0.1 microliter/min. We further investigated the effects of intraseptal microinfusions or systemic infusions of the gamma-melanocyte-stimulating hormone (gamma-MSH), a derivative of the proopiomelanocortin, on LPS-induced fever. Intraseptal microinfusions of gamma-MSH at a concentration of 10(-5) mol/l for 6 h with an infusion speed of 0.1 microliter/min caused a 38% reduction in fever. A significantly greater 57% reduction in fever was observed when the intraseptal microinfusion of gamma-MSH was combined with electrical stimulation of the PVN (for parameters see above). A systemic infusion of 0.261 mumol gamma-MSH for 6 h reduced LPS fever to approximately 50% compared with animals infused with vehicle (0.9% saline).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Antipyresis caused by stimulation of vasopressinergic neurons and intraseptal or systemic infusions of gamma-MSH. 814 22

Septic shock results from excessive stimulation of the host immune system, especially macrophages, by lipopolysaccharide (LPS), or endotoxin, which resides on the outer membrane of bacteria. Protein tyrosine kinase inhibitors of the tyrphostin AG 126 family protect mice against LPS-induced lethal toxicity. The protection correlates with the ability of these agents to block LPS-induced production of tumor necrosis factor alpha (TNF-alpha) and nitric oxide in macrophages as well as LPS-induced production of TNF-alpha in vivo. Furthermore, this inhibitory effect correlated with the potency of AG 126 to block LPS-induced tyrosine phosphorylation of a p42MAPK protein substrate in the murine macrophage.
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PMID:Prevention of lipopolysaccharide-induced lethal toxicity by tyrosine kinase inhibitors. 819 Dec 85

Nitric oxide (NO) formation via the expression of an endotoxin- and cytokine-inducible NO synthase (iNOS) within the vascular smooth muscle is thought to be responsible for the cardiovascular collapse that occurs during septic shock and antitumor therapy with cytokines. Because the molecular mechanisms that underlie induction of iNOS are still unclear and because tyrosine kinases are implicated in interleukin-1 beta (IL-1 beta)-induced prostaglandin synthesis in mesangial cells and in NO generation by an insulinoma cell line, we investigated the influence of tyrosine kinase inhibitors on iNOS induction in cultured rat aortic smooth muscle cells (RASMC). The production of biologically active NO was demonstrated by L-arginine-dependent guanosine 3',5'-cyclic monophosphate (cGMP) accumulation after a 3-h exposure to either IL-1 beta or lipopolysaccharide (LPS). Pretreatment of RASMC for 30 min with the tyrosine kinase inhibitor genistein prevented both IL-1 beta- and LPS-elicited cGMP accumulation in a concentration-dependent manner. Geldanamycin, a chemically different tyrosine kinase inhibitor, also blocked cGMP formation in response to both LPS and IL-1 beta at nanomolar concentrations. Genistein and geldanamycin inhibited cGMP accumulation even when added 90 min after LPS exposure, but no inhibition was observed when they were included at later time points (120-180 min), suggesting that the inhibitors had no direct effect on iNOS activity after its induction. Formation of cGMP in response to sodium nitroprusside and to NO released from bovine aortic endothelial cells remained virtually unaffected by genistein and geldanamycin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Tyrosine kinase inhibitors suppress endotoxin- and IL-1 beta-induced NO synthesis in aortic smooth muscle cells. 821 7

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


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