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)

Interleukin-6 (IL-6) is a multifunctional cytokine that regulates various aspects of the immune response, acute-phase reaction and haematopoiesis (for reviews see refs 1, 2). In vitro, leukaemia inhibitory factor, oncostatin M, ciliary neurotrophic factor and interleukin-11 display overlapping activities with IL-6. This functional redundancy may be explained by the interactions of specific binding receptors with a common signal-transducing receptor (gp130) (for reviews see refs 3, 4). To elucidate the unique function of IL-6 in vivo, we have disrupted the IL-6 gene by homologous recombination. IL-6-deficient mice develop normally. They fail to control efficiently vaccinia virus and infection with Listeria monocytogenes, a facultative intracellular bacterium. The T-cell-dependent antibody response against vesicular stomatitis virus is impaired. Further, the inflammatory acute-phase response after tissue damage or infection is severely compromised, whereas it is only moderately affected after challenge with lipopolysaccharide. We conclude that IL-6 production induced by injury or infection is an important in vivo SOS signal which coordinates activities of liver cells, macrophages and lymphocytes.
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PMID:Impaired immune and acute-phase responses in interleukin-6-deficient mice. 812 68

While lipopolysaccharide endotoxin is the most prominent inducer of the kinecascade (TNF alpha, IL-1, 4, 6, 8) that leads to shock and multiple organ failure, bacterial exotoxins and products of certain gram positive bacteria can induce the same end results. We theorize that more than one pathogen can induce the sequence of protooncogene activation and growth factor release that results in the formation of KS. If KS has its own unique viral etiology, this virus has not as yet been isolated or identified but we continue to search for it. However, it is entirely possible that these lesions do not have a single well-defined etiologic agent but are the result of multiple agents cooperating in a set sequence. An endogenous, or apathogenic exogenous, retrovirus may replace HIV for initiator growth factor induction in CD4 cells in the classical (Mediterranean) or iatrogenic disease; and other pathogens co-exist or sequentially replace each other in the African endemic disease; whereas an array of viral pathogens (prominent among them CMV) take over growth factor induction in endothelial cells proliferating in response to the initiator growth factor (oncostatin M) released from HIV-infected CD4 lymphocytes in AIDS-KS.
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PMID:Multiple pathogens may induce growth factor cascade resulting in KS. 823 2

A sensitive and specific enzyme immunoassay was developed for detecting oncostatin M (OM) in human plasma and serum. The assay utilizes three anti-OM monoclonal antibodies that recognize mutually exclusive epitopes, including a neutralizing epitope. A sensitivity of 24 pg/ml was routinely obtainable. The assay showed no cross-reactivity with leukemia inhibitory factor (LIF) or interleukin-6 (IL-6), other members of the cytokine family that includes OM. The utility of the enzyme immunoassay (EIA) was demonstrated by detecting the time-dependent accumulation of OM in plasma from lipopolysaccharide (LPS)-treated human whole blood. The concentration of OM in human sera from normal donors was generally below the detection limits of the assay. However, concentrations of OM greater than 25 pg/ml were found in 17 of 212 serum samples from apparently normal donors. The detection of OM in human plasma and serum demonstrates that the EIA could be a useful tool in examining the role of OM in physiologic and pathologic states.
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PMID:Detection of oncostatin M in human plasma and serum by a sensitive enzyme immunoassay. 834 66

A panel of cytokines was tested for inhibitors of interleukin-6 (IL-6)-dependent cell proliferation. Murine type I and II interferons (mIFNs) strongly inhibited proliferation of IL-6-dependent B9 and 7TD1 cells in a dose-dependent manner. Human tumor necrosis factor-alpha (hTNF-alpha) and human transforming growth factor-beta (hTGF-beta) potently inhibited B9 and to a lesser extent 7TD1 cells, while hIL-11, human oncostatin M (hOSM), and human leukemia inhibitory factor (hLIF) had no inhibitory effects on IL-6-dependent growth. Conversely, IL-11 and OSM but not LIF stimulated B9 and 7TD1 cell growth. However, compared with IL-6, up to 1000-fold higher IL-11 and OSM concentrations were required to induce maximal cell proliferation. Increasing concentrations of IL-6 (up to 100 ng/ml) could not overcome the antiproliferative effects of mIFNs, hTNF-alpha and hTGF-beta. Supernatants from mIFN-gamma and lipopolysaccharide (LPS)-treated mouse macrophages (ANA-1 cell line) were tested in B9 cell assays to identify cytokines among stimulatory and inhibitory biological activities that can inhibit IL-6-dependent proliferation. Undiluted or relatively concentrated supernatants from ANA-1 macrophages treated with mIFN-gamma and/or LPS did not contain detectable IL-6 bioactivity. However, diluted samples contained considerable amounts of detectable IL-6 bioactivity (nanogram levels). Testing the same samples for IL-6 immunoreactivity using enzyme-linked immunoabsorbent assay revealed comparable levels of mIL-6. We conclude that IFNs, TNF-alpha, and TGF-beta and possibly other factors are potent, dominant inhibitors of IL-6-dependent plasmacytoma/hybridoma growth in vitro.
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PMID:Multiple cytokines inhibit interleukin-6-dependent murine hybridoma/plasmacytoma proliferation. 859 34

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

Cardiotrophin-1 (CT-1) is a member of the gp130 family of cytokines that includes interleukin-6, interleukin-11, ciliary neurotrophic factor, leukemia inhibitory factor, and oncostatin M. As interleukin-6, leukemia inhibitory factor, and ciliary neurotrophic factor were previously reported to inhibit the production of tumor necrosis factor (TNF), we studied the effect of CT-1 on serum and heart TNF levels in mice treated with lipopolysaccharide (100 ng/mouse, iv). Co-treatment with CT-1 (5 micrograms/mouse intravenously) markedly inhibit TNF production both in serum and in the heart. The effect of CT-1 seems to be direct as it also inhibited TNF production when added to whole mouse blood cultured with lipopolysaccharide. Thus, CT-1 might play a protective role in some TNF-mediated diseases.
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PMID:Cardiotrophin-1 inhibits tumor necrosis factor production in the heart and serum of lipopolysaccharide-treated mice and in vitro in mouse blood cells. 895 22

We have investigated the function of different mediators of the regulation of the human C-reactive protein (hCRP) gene in transgenic mice. hCRP was induced by lipopolysaccharide and wounding in interleukin-6 (IL-6) +/+ mice, but not in IL-6 -/- mice. This finding suggested that IL-6 is necessary for the induction of hCRP. However, injection of IL-6 did not induce the hCRP gene. Thus, the induction of hCRP by IL-6 seems to require an additional cofactor. Therefore, we screened different cytokines for their activity in IL-6 +/+ and IL-6 -/- mice. Surprisingly, interleukin-1beta, as well as oncostatin M or leukaemia inhibitory factor, led to an induction of hCRP in both genetic backgrounds. These results indicate an IL-6-dependent and -independent regulation of hCRP. These hCRP transgenic mice therefore represent a novel model system for defining the cytokine network involved in the regulation of acute-phase genes during the course of inflammation.
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PMID:Interleukin-6-dependent and -independent regulation of the human C-reactive protein gene. 935 11

The present investigation was carried out to study the effect of aging on the activation of murine peritoneal macrophages by lipopolysaccharide (LPS) plus interferon-gamma (IFN-gamma) to tumoricidal state. Age-dependent alteration in macrophage-mediated tumor cell binding, cytotoxicity, cytostasis and production of the tumoricidal effector molecules oncostatin M, tumor necrosis factor and nitric oxide (NO) was studied. Macrophages (1.5 x 10(5)) obtained from mice of different age groups were separated on the basis of the reproductive status of the mice into prereproductive (young), reproductive (adult) and postreproductive (old) for studying their activation. Macrophages obtained from the old mice were found to be least responsive to the activation signal of LPS + IFN-gamma for macrophage-mediated tumoricidal activity and production of effector molecules. The macrophages of the old mice did not express inducible nitric oxide synthase, an enzyme responsible for the production of NO by activated macrophages. Macrophages of the adult and young groups showed better response; however, optimal response was observed in the macrophages of adult mice. The reasons for the observed difference in the response of macrophages are discussed.
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PMID:Effect of aging on the tumoricidal functions of murine peritoneal macrophages. 952 80

Cardiotrophin-1 (CT-1) is a recently discovered member of the gp130 cytokine family, which includes IL-6, IL-11, leukemia inhibitory factor, ciliary neurotrophic factor, and oncostatin M. Recent evidence suggests that, like other members of this family, CT-1 may possess anti-inflammatory properties. We hypothesized that in vivo CT-1 administration would attenuate endotoxin (ETX)-induced acute lung injury. We studied the effects of CT-1 (100 microgram/kg ip, 10 min prior to ETX) in a rat model of ETX-induced acute lung injury (Salmonella typhimurium lipopolysaccharide, 20 mg/kg ip). Six hours after ETX, lungs were harvested for determination of neutrophil accumulation (myeloperoxidase, MPO, assay) and lung edema (wet-to-dry weight ratio). Mechanisms of pulmonary vasorelaxation were examined in isolated pulmonary artery rings at 6 h by interrogating endothelium-dependent (response to acetylcholine) and endothelium-independent (response to sodium nitroprusside) relaxation following alpha-adrenergic (phenylephrine)-stimulated preconstriction. CT-1 abrogated the endotoxin-induced lung neutrophil accumulation: 2.3 +/- 0.2 units MPO/g wet lung (gwl) vs 6. 3 +/- 0.3 units MPO/gwl in the ETX group (P < 0.05 vs ETX, P > 0.05 vs control). Similarly, CT-1 prevented ETX-induced lung edema: wet-to-dry-weight ratio, 4.473 +/- 0.039 vs 4.747 +/- 0.039 in the ETX group (P < 0.05 vs ETX, P > 0.05 vs control). Endotoxin caused significant impairment of both endothelium-dependent and -independent pulmonary vasorelaxation, and CT-1 attenuated this injury. Thus, cardiotrophin-1 possesses significant anti-inflammatory properties in a model of endotoxin-induced acute lung injury.
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PMID:Cardiotrophin-1 attenuates endotoxin-induced acute lung injury. 1035 26

We used in vitro and in vivo approaches to examine whether tumor necrosis factor-alpha (TNF-alpha) and oncostatin M (OSM), cytokines that bind to distinct classes of receptors, differentially regulate expression of P- and E-selectin in murine and primate endothelial cells. In human umbilical vein endothelial cells, TNF-alpha rapidly increased mRNA for E-selectin but not P-selectin. OSM elicited little or no change in mRNA for E-selectin, but induced a delayed and prolonged increase in P-selectin mRNA. TNF-alpha and OSM did not cooperate to further enhance P- or E-selectin mRNA. Intravenous infusion of Escherichia coli, which markedly elevates plasma lipopolysaccharide and TNF-alpha, increased mRNA for E-selectin but not P-selectin in baboons. In murine bEnd.3 endothelioma cells, TNF-alpha and OSM individually and cooperatively increased mRNA and protein for both P- and E-selectin. Intravenous injection of these cytokines also individually and cooperatively increased mRNA for P- and E-selectin in mice. We conclude that the murine P- and E-selectin genes respond to both TNF-alpha and OSM, whereas the primate P- and E-selectin genes have much more specialized responses. Such differences should be considered when extrapolating the functions of P- and E-selectin in murine models of inflammation to humans.
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PMID:Divergent inducible expression of P-selectin and E-selectin in mice and primates. 1057 97


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