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)

Solid-phase enzyme immunoassays (with high-turnover acetylcholinesterase as label) for human IL-1 alpha and IL-1 beta were applied to quantify the production of these factors by cultured human umbilical vein endothelial cells (HUVECs). Immunoreactive IL-1s exhibited a typical pattern in HUVECs, under either basal or stimulated conditions: the alpha form was predominant over the beta form and the cell-associated IL-1s measured were more abundant than the material recovered in the supernatants. Bacterial lipopolysaccharide (LPS, 0.5-5 micrograms/ml) significantly increased the basal production of IL-1. Pulses of recombinant IL-1 alpha or -beta or of TNF-alpha followed by a 24 h culture period were also associated with an increased endothelial production of IL-1, with a higher proportion of material secreted in the supernatants as compared with LPS. Other cytokines applied as pulses failed to induce the IL-1s or to modify LPS-induced production of IL-1: they include IL-2, immune interferon, GM-CSF, TGF-beta and EGF. Pharmacological modulators of LPS-induced IL-1 production were identified: glucocorticoids were inhibitors whereas retinoic acid and 1.25-dihydroxy-vitamin D3 had no effects and prostaglandin E2 and IBMX were weak inhibitors. There is no evidence that IL-1 alpha and IL-1 beta are regulated differently in HUVECs, but several significant differences from the monocyte were observed in the regulation of HUVEC IL-1 production.
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PMID:Pharmacological modulation of interleukin 1 production by cultured endothelial cells from human umbilical veins. 169 6

We have shown that certain murine tumors grow more slowly and spread less readily in immune deficient animals. We have also demonstrated that immunologic factors explain certain aspects of this difference. In the work presented we demonstrate that a subpopulation of splenocytes produce a factor(s) that enhances tumor cell proliferation in vitro. We also describe an in vitro model to determine the level of tumor stimulatory activity. We found that the tumor cell growth-enhancing activity (TEA) is heat stable but sensitive to trypsin digestion, low pH and beta-mercaptoethanol. TEA production is found to be insensitive to mitogen stimulation such as concanavalin A, lipopolysaccharide, and phytohemagglutinin. Among the known growth factors and interleukins we have tested (interleukin 1-7, basic FGF, EGF, TGF-beta PDGF, GM-CSF, and MCSF), none appear to account for TEA activity.
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PMID:Initial description of a tumor enhancing activity produced by murine splenocytes. 188 89

The expression of the early genes JE and KC has been examined in Balb/C 3T3 cells treated with bacterial lipopolysaccharide (LPS). Previous studies showed that JE and KC mRNAs are induced in murine peritoneal macrophages treated with LPS, suggesting a role for these genes in inflammatory responses. Consistent with this possibility are recently published cDNA sequences which document that both genes are members of a superfamily of inflammation- and/or growth-related cytokines. In the present study, we provide evidence that the mRNAs for JE and KC are specifically induced by LPS treatment of Balb/c 3T3 cells. The LPS-stimulated expression of JE and KC was dose dependent, and exhibited a transient time course; message levels were maximal between 2 and 4 hr and declined by 8 hr. The LPS-augmented accumulation of JE and KC occurred even in the presence of cyclohexamide, which additionally had a superinducing effect on the expression of both genes. Cyclohexamide alone, in the absence of LPS, also induced JE and KC mRNA accumulation. LPS-stimulated JE and KC mRNA expression was dependent upon the stimulation of transcription as determined by nuclear "run-on" studies. Comparative analyses indicated that, under the conditions employed, LPS was a somewhat less effective stimulant of JE expression than PDGF or EGF, and was more effective than PDGF and equivalent to EGF in its ability to augment KC accumulation. Unlike PDGF and EGF, LPS did not stimulate DNA synthesis by Balb/c 3T3 cells at any time over the 72 hr period examined. The ability of the inflammatory, non-mitogenic stimulus LPS to selectively induce JE and KC mRNA expression by fibroblasts may reflect their participation in inflammation and wound healing as secretory cells.
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PMID:Lipopolysaccharide induces competence genes JE and KC in Balb/C 3T3 cells. 211 13

1 The mechanisms by which agents modulate the induction of kinin B1-receptors were investigated by studying the effects of kinins in vitro, by use of the rabbit isolated aorta, and in vivo by measuring the blood pressure of anaesthetized rabbits. 2 The contractile response of the rabbit isolated aorta to kinins increased in a time-dependent manner in vitro. This effect was abolished by continuous exposure to the protein synthesis inhibitor cycloheximide (71 microM). 3 Several substances were found to increase specifically the rate of sensitization to des-Arg9-bradykinin (des-Arg9-Bk), when applied continuously in vitro to tissues isolated from normal animals: bacterial lipopolysaccharide (LPS; 1 micrograms ml-1), muramyl-dipeptide (MDP; 2 micrograms ml-1), phorbol myristate acetate (PMA; 320 nM), epidermal growth factor (EGF; 100 ng ml-1) and endothelial cell growth factor (150 micrograms ml-1). 4 The protease inhibitors phenylmethylsulphonyl fluoride and aprotinin, a non-adjuvant isomer of MDP, rabbit purified leukocyte interferon, fibroblast growth factor and the chemotactic peptide N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP) did not have this effect. 5. It has been demonstrated that LPS induces B1-receptors in rabbits enabling des-Arg9-Bk to act as a hypotensive agent. In these experiments neutropenia induced by nitrogen mustard, did not prevent the in vivo effect of LPS. MDP (300 micrograms) and PMA (100 micrograms) were also found to induce a state of responsiveness to des-Arg9-Bk in vivo. FMLP (1 mg i.v.) induced a temporary decrease in blood neutrophil counts but had no effect on the induction of responses to des-Arg9-Bk. 6. The development of responses mediated by the B,-receptor in the two experimental systems seems to be unrelated to the activation of neutrophil leukocytes, but may be related to the activation of tissue macrophages. Approximately 3% of cultured adherent cells derived from rabbit aorta strips following protease digestion were stained for non-specific esterase, supporting such a possibility.
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PMID:Studies on the induction of pharmacological responses to des-Arg9-bradykinin in vitro and in vivo. 367 93

Liver cells express a wide range of extracellular receptors involved in the control of cell growth and arrest that can be studied ex vivo. Incubation of primary cultures of hepatocytes with IL-1 beta, TNF-alpha or lipopolysaccharide promotes the expression of the inducible form of nitric oxide synthase and NO release, a process that is inhibited to a different extent by incubation of the cells with EGF. In addition to this growth factor, IL-6 and TGF-beta also inhibited NO synthesis. Therefore, EGF by itself or in combination with other cytokines may be involved in the down-regulation of the NO synthesis that occurs in the early steps of liver regeneration.
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PMID:Epidermal growth factor inhibits cytokine-dependent nitric oxide synthase expression in hepatocytes. 754 5

Interleukin 1 receptor antagonist (IL-1ra) is induced in monocytes stimulated with lipopolysaccharide (LPS) or cultured on adherent immunoglobulin G (IgG). We examined the effects of various cytokines on monocyte IL-1ra protein production and compared it to IL-1 beta, which is regulated differently. IL-3 and GM-CSF induced near equivalent amounts of IL-1ra protein as does LPS. IL-1 alpha and IL-4 were weaker inducers. IL-3 and GM-CSF did not affect LPS or IgG induction of IL-1ra or LPS-induced IL-1 beta. However, our data confirmed that IL-4 up-regulated LPS-induced IL-1ra and down-regulated LPS-induced IL-1 beta. The kinetics of IL-1ra production by monocytes varied between stimulation with adherent IgG and cytokines or LPS. Cells cultured on adherent IgG exhibited a higher level of and more prolonged IL-1ra production. Relative IL-1ra mRNA levels after 8 h were in the order: adherent IgG > LPS or GM-CSF > IL-1 alpha, IL-3 or IL-4. The following cytokines failed to induce IL-1ra production: IL-2, IL-6, G-CSF, M-CSF, IFN-gamma, TGF beta 1, TGF beta 2, TNF alpha, acidic and basic FGF, PDGF and EGF. These results suggest that IL-1 alpha, IL-3, IL-4 and GM-CSF may play important roles in regulating monocyte IL-1ra production and that different mechanisms may be involved in induction of IL-1ra by adherent IgG in comparison to LPS or other cytokines.
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PMID:Interleukin 1 receptor antagonist production in human monocytes is induced by IL-1 alpha, IL-3, IL-4 and GM-CSF. 814 95

Previous studies from our laboratory suggested that phorbol 12-myristate 13-acetate (TPA) stimulates prostaglandin E2 (PGE2) production by inducing de novo synthesis of prostaglandin H synthase (PHS) in a rat tracheal cell line. We report here an extension of this work to further elucidate the mechanisms by which TPA (and epidermal growth factor) stimulates PGE2 production. We used the rat tracheal cell line EGV6, which has a lower basal level of PGE2 production and responds to TPA and EGF stimulation with a much greater increase in PGE2 synthesis than the previously used cell line, Incubation of EGV6 cultures with TPA or EGF resulted in a time- and dose-dependent increase in PGE2 synthesis up to 40-fold and 6-fold, respectively. Serum also stimulated PGE2 synthesis, while bombesin, retinoic acid, and bacterial lipopolysaccharide did not. PHS protein levels in microsomal preparations from the cells were estimated by Western analysis. Antibodies raised against murine PHS-2 cross reacted with the EGV-6 PHS while several antibody preparations that react with PHS-1 from ram or mouse reacted poorly with the cellular preparation. TPA treatment increased the de novo synthesis of PHS-2 while dexamethasone treatment reduced the response to TPA. Northern blot analysis of mRNA from EGV6 cultures using a ram PHS cDNA revealed a 2.8- and a 4.5- to 4.9-kb (designated 4.9 kb) transcript. Treatment with TPA or EGF increased the expression of both transcripts and this effect was further enhanced by cyclohexamide. To further define the PHS mRNA species of EGV6 cells, two well-characterized murine PHS cDNA probes were used. The constitutive murine PHS cDNA probe hybridized only with the 2.8-kb transcript, and the inducible murine PHS cDNA hybridized only with the 4.9-kb transcript. The rates of induction as well as degradation of the 4.9-kb PHS mRNA were much more rapid than those of the 2.8-kb mRNA species. Dexamethasone partially inhibited the induction of both PHS transcripts by TPA. Southern analysis of genomic EGV6 DNA indicated the presence of two distinct PHS genes in these cells. Taken together these findings indicate that two PHS genes are expressed in rat tracheal epithelial cells. In contrast to the PHS genes expressed in murine (and chicken) fibroblasts in which only the gene coding for the larger mRNA species is transcriptionally regulated, in the rat tracheal cells both genes are positively regulated by TPA and EGF and downregulated by glucocorticoids.
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PMID:Phorbol ester and epidermal growth factor enhance the expression of two inducible prostaglandin H synthase genes in rat tracheal epithelial cells. 832 87

The synthesis of induced nitric oxide (NO) is regulated by several cytokines, including growth factors produced following hepatic injury and inflammation. However, little information is available on the role of growth factors in regulating the inducible NO synthase in human hepatocytes. The capacity of hepatocellular mitogens (HGF, EGF, and TGF-alpha) to regulate the inducible NO synthase (iNOS) was studied in human hepatocytes incubated with inflammatory cytokines and lipopolysaccharide (LPS). Furthermore, the effects of hepatic mitogens on NO-induced changes in DNA and protein synthesis was studied. It was found that NO-mediated decrease of protein and DNA synthesis were partially reversed by the mitogens. This was associated with a down-regulation in cytokine-mediated hepatocyte NO formation, iNOS mRNA expression, and NOS enzyme activity. Cytokine-induced NO formation or SNAP, an NO donor, added with cytokines increased hepatocyte chromatin condensation but no DNA fragmentation was observed. The increase in chromatin condensation was partially reversed by hepatic mitogens and corresponded with the inhibition of NO production. Thus, the hepatic mitogens, HGF, EGF, and TGF-alpha, all suppress iNOS expression and it is the suppression of iNOS that appears to be responsible for the mitogen-reduced preservation of DNA and protein synthesis and prevention of chromatin condensation.
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PMID:Effects of hepatocellular mitogens on cytokine-induced nitric oxide synthesis in human hepatocytes. 883 Jul 95

Quiescent and non-quiescent human gingival fibroblasts (HGF) were incubated for 24 hours with Actinobacillus actinomycetemcomitans lipopolysaccharide (LPS) and/or growth factors (interleukin-1 beta [IL-1 beta], insulin, epidermal growth factor [EGF], platelet-derived growth factor [PDGF], fibroblast growth factor [FGF], and transforming growth factor-beta [TGF-beta]) to examine the ability of LPS to modify HGF proliferation in response to these autocrine and paracrine growth factors. A. actinomycetemcomitans LPS at high concentrations (> or = 9 micrograms/well) generally resulted in a reduction in DNA synthesis in quiescent and non-quiescent fibroblasts; however, LPS at low concentrations (< 9 micrograms/well) showed a minimal enhancement of DNA synthesis (40 to 60%) in quiescent and non-quiescent cells. HGF co-incubated with mitogenic agents and LPS (9 micrograms/well) exhibited suppression of growth factor-induced 3H-Tdr uptake compared to growth factor-stimulated controls. In contrast, 3H-Tdr uptake was slightly elevated with addition of LPS at low concentrations (0.09 microgram/well). These trends were seen with all growth factors tested. Non-quiescent cells, in general, were more responsive to the growth factors and LPS/growth factor combinations when compared to the quiescent HGF. HGF were further tested for the ability of LPS to alter growth factor responsiveness by pretreating the cells with LPS prior to incubation of the growth factor, as well as, subsequent addition of LPS to growth factor-pretreated cells. Similar patterns were observed as above, except IL-1 beta-pretreated quiescent and non-quiescent HGF followed by LPS addition demonstrated a marked elevation in proliferation when compared to IL-1 beta stimulated controls. These findings suggest that LPS may potentially modulate the proliferative rate of connective tissue undergoing inflammatory or growth factor-induced reparative processes in periodontal lesions.
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PMID:The effect of lipopolysaccharide on growth factor-induced mitogenesis in human gingival fibroblasts. 899 73

Hepatocellular mitogen (HGF and EGF) inhibited lipopolysaccharide and cytokine mixture (referred as LPS/CM)-induced NO synthesis and cellular injury in hepatocytes. Mitogenic inhibitors such as hydroxyurea and Wortmannin could not reverse EGF or HGF-inhibited NO production, whereas both of them showed some inhibitory effect on hepatocyte NO synthesis. Although activation of protein kinase C (PKC) by phorbol 12-myristate 13-acetate (PMA) had no effect on hepatocyte NO synthesis, deletion of PKC activity by long-term treatment of hepatocytes with PMA abolished LPS/CM-induced NO production. In addition, pretreatment of hepatocytes with HGF and EGF also blocked LPS/CM-induced NO synthesis in the hepatocyte. These results suggest that proliferating signal is not directly involved in mitogen-inhibited NO synthesis in the hepatocyte, and LPS/CM-mediated NO synthesis is associated with the metabolic/redox state of hepatocytes.
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PMID:Mitogenic-factor-dependent regulation of lipopolysaccharide and cytokine mixture-mediated hepatocyte nitric oxide synthesis in vitro. 950 Oct 15


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