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)

Splenocytes cultured for 24 h in the presence of interleukin-2 (IL-2), lipopolysaccharide (LPS) or both together expressed a cytotoxic activity against the YAC-1 lymphoma cell line and to a lesser extent against P815 mastocytoma cells. The association of IL-2 and LPS had an additive effect on induction of cytotoxicity. The IL-2-induced cytotoxic activity lasted for the whole of the culture; however, the addition of LPS at the initiation of the culture increased the cytotoxic activity during its the early phase, the increment being followed by a fall of lytic activity after 72 h of culture. Assessment of interferon (IFN) in the culture supernatants showed (a) a production of IFN gamma by IL-2-supplemented cultures, (b) a more potent IFN production by cultures treated with IL-2 plus LPS (including 20% IFN alpha/beta, (c) and that indomethacin (1 microM) potentiated the effect of either IL-2 or LPS used alone but did not significantly increase the cytotoxic activity of cultures treated with IL-2 plus LPS (the one that produced a high level of IFN). When cultures were treated by an anti-IFN gamma antibody we observed no change in the cytotoxic activity; however, in the presence of anti-IFN alpha/beta serum the cytotoxic activity of cultures treated with IL-2 plus LPS was inhibited after 24 h but stimulated after 72 h. When cultures treated with IL-2 plus LPS were supplemented with both indomethacin and anti-IFN alpha/beta the cytotoxic activity assessed after 72 h of culture was maintained at the same level as that of IL-2-treated cultures, hence the fall after 72 h of the cytotoxicity of cultures initiated in the presence of LPS alone was affected by both the immune serum and the cyclooxygenase inhibitor. Altogether these data show that when splenocytes are cultured for more than 72 h in the presence of IL-2 and LPS their cytotoxic activity decreases, and it is likely that this diminution is linked to the endogenous production of prostaglandin E2 and INF alpha/beta.
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PMID:Effects of lipopolysaccharide on interleukin-2-induced cytotoxic activity of murine splenocyte cultures: role of prostaglandin E2 and interferons. 138 57

Recently, we have isolated and characterized a set of cDNA clones which encode lipopolysaccharide-inducible proteins in murine peritoneal macrophages. Here, we report the sequence and identification of one of these cDNAs previously termed C7. Nucleotide sequence analysis revealed an open reading frame encoding a predicted polypeptide composed of 98 amino acids, which contained a 21 amino acid residue signal peptide, indicating approximately 9 kDa of mature protein. The deduced protein sequence showed homology (67% identity, 77% considering conservative amino acid changes) with the human INF gamma-inducible gene IP-10, a member of the recently described superfamily of chemotactic and mitogenic proteins which includes platelet factor 4, monocyte-derived neutrophil chemotactic factor (NAF, NAP-1, IL-8), and MGSA/gro/KC. Thus C7 would appear to represent the murine homologue of the human IP-10 gene or a very closely related gene.
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PMID:A macrophage LPS-inducible early gene encodes the murine homologue of IP-10. 218 6

The cytokine IFN beta 2/IL-6 has recently been shown to regulate the expression of genes encoding hepatic acute phase plasma proteins. INF beta 2/IL-6 has also been shown to be identical to MGI-2, a protein that induces differentiation of bone marrow precursor cells toward mature granulocytes and monocytes. Accordingly, we have examined the effect of IFN beta 2/IL-6 on expression of the IL-1- and tumor necrosis factor-unresponsive acute phase protein alpha 1-antitrypsin (alpha 1 AT) in human hepatoma-derived hepatocytes and in human mononuclear phagocytes. Purified human fibroblast and recombinant IFN beta 2/IL-6 each mediate a specific increase in steady-state levels of alpha 1 AT mRNA and a corresponding increase in net synthesis of alpha 1 AT in primary cultures of human peripheral blood monocytes as well as in HepG2 and Hep3B cells. Thus, the effect of IFN beta 2/IL-6 on alpha 1 AT gene expression in these cells is primarily due to an increase in accumulation of alpha 1 AT mRNA and can be distinguished from the direct, predominantly translational effect of bacterial lipopolysaccharide on expression of this gene in monocytes and macrophages. The results indicate that IFN beta 2/IL-6 regulates acute phase gene expression, specifically alpha 1 AT gene expression, in extrahepatic as well as hepatic cell types.
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PMID:Interferon beta 2/interleukin 6 modulates synthesis of alpha 1-antitrypsin in human mononuclear phagocytes and in human hepatoma cells. 247 25

The production of interferon-alpha/beta (INF-alpha/beta) and interferon gamma (IFN-gamma) in NOD and ICR mice was studied in vitro and in vivo. The in vitro IFN-alpha/beta production in the spleen cells of NOD mice, which were stimulated with either Newcastle disease virus (NDV), Sendai virus, poly(I:C) or lipopolysaccharide (LPS), was very similar to the IFN-alpha/beta production in the spleen cells of ICR mice. Contrastingly, the in vitro IFN-gamma production in the spleen cells of NOD mice, which were stimulated with either concanavalin A (Con A), phytohemagglutinin (PHA) or pokeweed mitogen (PWM), was greater than the IFN-gamma production in spleen cells of ICR mice. The in vivo IFN-alpha/beta production in NOD mice induced by NDV was also very similar to that in ICR mice, whereas the in vivo IFN-gamma production in the BCG-sensitized NOD mice, which was induced by purified protein derivative (PPD), was greater than that in the ICR mice. These results may indicate that NOD mice have abnormalities on the IFN-gamma production.
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PMID:In vitro and in vivo interferon production in NOD mice. 251 17

Serum from lipopolysaccharide-treated mice (postendotoxin serum, PES) induces the differentiation of M1 myeloid leukemia cells into mature macrophages, as well as supporting the proliferation of the interleukin 6 (IL6)-dependent B9 hybridoma cells. The kinetics of appearance of these two activities in PES were identical. To determine whether these two activities are due to the presence of the same substance, we tested whether anti-IL6 antibodies could neutralize the differentiation-inducing activity of PES. We found that anti-IL6 antibodies completely neutralized the proliferation of B9 cells and resulted in a 60% neutralization of the differentiation-inducing activity of PES. Anti-interferon alpha/beta (INF alpha/beta) antibodies neutralized 70% of the differentiation-inducing activity of PES. These data suggest that the differentiation-inducing activity of PES is not limited to IL6, and that PES contains additional factors such as INF alpha/beta that are capable of inducing differentiation of M1 cells.
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PMID:Interleukin 6 (interferon beta 2) and interferon alpha/beta present in postendotoxin serum induce differentiation of murine M1 myeloid leukemia cells. 268 77

The J2 recombinant retrovirus expressing v-myc/v-raf (also known as MYC/RAF1) immortalized macrophages from the bone marrow of lipopolysaccharide-responsive mouse strains, producing the ANA-1 cell line from C57BL/6 mice and the INF-3A cell line from C3H/HeN mice. In contrast, J2 recombinant retrovirus infection of the fetal liver from C57BL/6-Ly-5a mice immortalized a cell line (GGD) that did not exhibit the characteristics of mature macrophages. The GGD cell line was classified as leukocytic on the basis of its expression of the Ly-6B.2, Fc gamma R, and Ly-5.2 antigens. Our results indicate that the J2 recombinant retrovirus selectively immortalizes macrophages from the bone marrow of C57BL/6 and C3H/HeN mice but immortalizes cells without definitive macrophage characteristics from murine fetal liver under the same culture conditions.
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PMID:Heterogeneity of hematopoietic cells immortalized by v-myc/v-raf recombinant retrovirus infection of bone marrow or fetal liver. 277 38

Murine macrophage hybridoma clones were established by fusing glycogen-elicited peritoneal exudate cells (glycogen-PEC) derived from C3H/HeN mice and the hypoxanthine-aminopterin-thymidine-sensitive murine macrophage cell line, J774.3-2. The macrophage hybridomas were further screened for the capacity to acquire tumoricidal activity upon stimulation with lipopolysaccharide (LPS) and recombinant interferon-gamma (IFN-gamma) using murine mammary adenocarcinoma MM48 cells as targets, and three macrophage hybridoma clones, KM-1, KM-2, and KM-3, were established. With concomitant stimulation with LPS, IFN-gamma activated these hybridomas dose dependently to exhibit high tumoricidal activity, whereas single stimulation with either INF-gamma or LPS, even with higher concentrations, did not activate the macrophage hybridomas. This contrasted with the activation of glycogen-PEC for eliciting tumoricidal activity with a single stimulation with LPS (greater than 1 ng/ml) or IFN-gamma (greater than 10 IU/ml). Thus, the macrophage hybridoma clones established here represent inflammatory macrophages which require both IFN-gamma and LPS for their activation.
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PMID:Establishment of murine macrophage hybridoma clones capable of acquiring tumoricidal activity upon activation with recombinant interferon-gamma and lipopolysaccharide. 311 Jan 75

Cellular constituents of heart muscle contain both constitutive and inducible nitric oxide (NO) signaling pathways that modulate the contractile properties of cardiac myocytes. The identities of the inducible NO synthase (iNOS) isoform(s) expressed in cardiac muscle, and of the specific cell types expressing iNOS activity, remain poorly characterized. We amplified a 217-base pair cDNA by reverse transcriptase-polymerase chain reaction from primary cultures of inflammatory cytokine-pretreated adult rat ventricular myocytes (ARVM) that was nearly identical to other iNOS cDNA sequences. Using this 217-base pair cDNA as a probe in Northern blots, we found no evidence of iNOS mRNA in control myocytes, but both interleukin-1 beta and interferon-gamma individually increased iNOS mRNA abundance in primary cultures of ARVM, with maximal expression at 12 h. The half-life of iNOS mRNA in actinomycin C1-treated cells was 4 h. Both dexamethasone and transforming growth factor-beta attenuated the induction of iNOS mRNA abundance and enzyme activity by IL-1 beta and INF gamma. Pretreatment with dexamethasone also abolished the induction of iNOS mRNA, but not the increase in GTP cyclohydrolase mRNA in purified cardiac myocytes from lipopolysaccharide-injected rats. In order to further characterize the specific cell type producing NO, we used a NO-specific porphyrinic/Nafion-coated microsensor to record NO release from a single, isolated ARVM pretreated with IL-1 beta and IFN gamma in L-arginine-depleted medium. NO release could be detected following microinjection of L-arginine in the vicinity of the cell juxtaposed to the NO microsensor, but not following microinjection of D-arginine, and not from ARVM pretreated with L-N-monomethylarginine. Cytokine-pretreated ARVM that had been maintained in L-arginine-depleted medium also exhibited a depressed contractile response to isoproterenol after addition of L-arginine, but not D-arginine. These results indicate that altered contractile function of cardiac myocytes following exposure to specific inflammatory cytokines is due to induction of myocyte iNOS.
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PMID:Cytokine-inducible nitric oxide synthase (iNOS) expression in cardiac myocytes. Characterization and regulation of iNOS expression and detection of iNOS activity in single cardiac myocytes in vitro. 752 57

Nitric oxide (NO) is a potent biological messenger molecule in the central nervous system (CNS). There are several potential sources of NO production in the CNS, including neurons and endothelial cells which express NO synthase (NOS) constitutively. Astrocytes and microglia can be induced by cytokines to express a NOS isoform similar to macrophage NOS (mNOS). Primary mixed glial cultures exposed to lipopolysaccharide (LPS) or a combination of LPS and gamma-interferon (INF-gamma) produce nitrite, a breakdown product of NO formation, in a dose-dependent manner. Nitrite production is detectable at 12 hr, peaks at 48 hr and is sustained for at least 96 hr. The NOS inhibitor, nitro-L-arginine (NArg), inhibits nitrite formation, but the immunosuppressant agent, FK506, does not. In mixed glial-neuronal cultures exposed to 50 ng LPS or 5 ng LPS and 1 microgram INF-gamma, neurons begin to die at 48 hr, approx. 24-36 hr after detectable nitrite production. Neurotoxicity is attenuated by 100 microM NArg. These data indicate that expression of inducible mNOS causes delayed neurotoxicity.
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PMID:Expression of inducible nitric oxide synthase causes delayed neurotoxicity in primary mixed neuronal-glial cortical cultures. 753 25

Evidence has previously been presented for an immunomodulatory role of a soluble activity, designated as tumor-derived recognition factor (TDRF), which was produced constitutively by P815 mastocytoma, L 1210 leukemia and other murine tumor targets. TDRF synergized with IFN-gamma and IL-2 to promote TNF-alpha and mRNA synthesis and release by murine macrophages for increased autocrine induction of nitric oxide (NO)-mediated tumor cytotoxicity. We have now further assessed the modulatory role of TDRF on TNF-alpha, TNF receptors (TNF-R) and NOS mRNA synthesis. Macrophages activated by INF-gamma priming and triggering by rTNF-alpha bacterial lipopolysaccharide (LPS) of IL-2 evoked greater NO generation in the presence than in the absence of L1210 targets. TDRF-containing culture fluid from L1210 targets was subsequently confirmed to synergize with IFN-gamma and rTNF-alpha, LPS or IL-2 triggering agents to promote increased TNF-alpha mRNA for autocrine induction of NOS mRNA synthesis with resultant augmentation of NO generation. IFN-gamma selectively upregulated TNF-R1 mRNA expression, whereas either IL-2 or LPS upregulated only TNF-R2 mRNA expression. TDRF combined with IFN-gamma to further upregulate TNF-R1 mRNA and with either IL-2 or LPS to further upregulate TNF-R2, mRNA expression. These findings indicate that TDRF activity synergizes with either IL-2 or LPS triggering agents for enhanced activation of IFN-gamma-primed macrophages by promotion of TNF-alpha and TNF-R mRNA synthesis for autocrine induction of NOS with resultant increased NO-mediated tumor cytotoxicity.
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PMID:Tumor-derived factor synergizes with IFN-gamma and LPS, IL-2 or TNF-alpha to promote macrophage synthesis of TNF-alpha and TNF receptors for autocrine induction of nitric oxide synthase and enhanced nitric oxide-mediated tumor cytotoxicity. 754 21


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