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)

Keratinocytes produce multiple cytokines in response to a variety of stimuli. The release of interleukin 1 (IL-1) from keratinocytes may be significant in initiation of cutaneous inflammation, and the presence of granulocyte/macrophage colony-stimulating factor (GM-CSF) is thought to be important in the regulation of antigen-presenting function by epidermal Langerhans cells. Because cyclosporin inhibits interleukin 2 release from T cells, it has been suggested that cyclosporin may function as an anti-inflammatory agent within the epidermis through inhibition of keratinocyte cytokine release. This investigation examined the direct effect of cyclosporin on the production of GM-CSF by murine keratinocytes and the keratinocyte cell line PAM 212. GM-CSF bioactivity increased in cell supernatants from keratinocytes exposed in vitro to 1 microgram/ml cyclosporin for up to 24 h. GM-CSF and IL-1 mRNA levels in keratinocytes cultured under similar conditions or in the presence of lipopolysaccharide also increased. The lack of inhibition of GM-CSF expression following cyclosporin treatment is consistent with recent observations in T cells and is opposite to the effect of cyclosporin on interleukin 2.
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PMID:Cyclosporin increases granulocyte/macrophage colony-stimulating factor (GM-CSF) activity and gene expression in murine keratinocytes. 154 36

Tumor necrosis factor-alpha (TNF-alpha), produced predominantly by activated monocytes/macrophages, inhibits leukemic cell growth and may contribute to a graft-versus-leukemia effect after marrow transplantation. We examined the recombinant cytokines interferon (IFN)-alpha, IFN-gamma, granulocyte- macrophage colony-stimulating factor (GM-CSF), and macrophage colony-stimulating factor (M-CSF), alone or in combination, for their ability to induce monocytes from normal donors and patients after marrow grafting to express TNF-alpha mRNA and secrete TNF-alpha bioactivity. Monocytes were isolated from peripheral blood by Percoll separation of E-rosette-negative cells, and cultured with cytokines under non-adherent, endotoxin-free conditions. TNF-alpha transcripts were undetectable in freshly isolated monocytes from normal donors. Only the combination of IFN-gamma/GM-CSF was consistently capable of inducing substantial TNF-alpha mRNA transcript levels and protein secretion. Levels of TNF-alpha transcripts induced by IFN-gamma/GM-CSF were maintained for at least 36 h, in contrast to lipopolysaccharide (LPS) stimulation which caused TNF-alpha mRNA levels to peak after 2 h and decline rapidly thereafter. IFN-gamma/GM-CSF was also capable of inducing a prolonged (at least 48 h) secretion of TNF-alpha bioactivity. In contrast, greater than 80% of the total TNF-alpha bioactivity secreted by LPS-stimulated monocytes was secreted in the first 8 h. When monocytes were incubated with IFN-gamma alone ('priming'), washed and then exposed to GM-CSF, both TNF-alpha mRNA expression and TNF-alpha protein production occurred.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regulation of tumor necrosis factor-alpha production and gene expression in monocytes. 161 21

We examined the responsiveness of two factor-dependent macrophage cell lines, BDM-1 and its subclone, BDM-1W3, to bacterial lipopolysaccharide (LPS), interferon-gamma (IFN-gamma), and tumor necrosis factor-alpha (TNF-alpha) for their growth. LPS inhibited the M-CSF-dependent proliferation of BDM-1 cells but it had no effect on the proliferation of BDM-1W3 cells. LPS promoted DNA synthesis and supported the cell viability in the absence of CSFs in BDM-1 and BDM-1W3 cells, suggesting that the intracellular signals are transduced from the interaction of LPS with LPS-binding sites in BDM-1W3 cells as well as in BDM-1 cells. IFN-gamma inhibited the proliferation of BDM-1 and BDM-1W3 cells. However, BDM-1 cells were more susceptible to the inhibitory effect of IFN-gamma than BDM-1W3 cells. In contrast to LPS and IFN-gamma, TNF-alpha did not inhibit the proliferation of BDM-1 and BDM-1W3 cells. These cell lines should be useful for studying the regulatory mechanisms in CSF-dependent macrophage proliferation.
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PMID:Differential effects of bacterial lipopolysaccharide and interferon-gamma on proliferation of two factor-dependent macrophage cell lines. 164 63

The colony-stimulating factors (CSF) belong to a group of proteins which regulate blood cell production. Human monocytes allowed to adhere express high levels of M-CSF transcripts and secreted protein at 24 h in the presence but not in the absence of indomethacin (Indo), an inhibitor of prostaglandin E (PGE) production. When induced with lipopolysaccharide (LPS), adherent monocytes express M-CSF, G-CSF, and GM-CSF transcripts and secrete these proteins and TNF. M-CSF and GM-CSF messages increase in LPS-induced monocytes by the addition of Indo, while G-CSF mRNA appears to decrease. Exogenous addition of PGE-2 to LPS-induced monocytes down-modulates the expression of M-CSF and GM-CSF transcripts. G-CSF message is elevated, suggesting an alternate pathway to G-CSF regulation. PGE-2 inhibits the secretion of CSFs and TNF. In contrast, LPS-induced monocytes held 24 h in nonadherent culture express G- and GM-CSF but not M-CSF. Monocytes that are adhered for 24 h and then treated with LPS for an additional 24 h express only M-CSF message and secrete M-CSF and TNF. PGE-2 added with LPS during the 24-48 h induction blocks M-CSF and TNF production, but appears to enhance M-CSF message expression, in contrast to its effect on 0 h inductions. These results suggest that adherence alone induces M-CSF gene expression, but low levels of PGE or other arachidonic acid metabolites limit this expression. Other events in 1 d-cultured monocytes block the ability to induce G-CSF and GM-CSF expression with LPS, and block the suppressive effect of PGE-2 on M-CSF expression at the RNA level.
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PMID:Differential expression of M-CSF, G-CSF, and GM-CSF by human monocytes. 168 60

The recent demonstration of the ability of human polymorphonuclear neutrophils (PMN) to secrete various cytokines in response to the granulocyte activator granulocyte-macrophage colony-stimulating factor (GM-CSF) but not to other cytokines, has led to the identification of PMN as biosynthetically active cells. In this study we have investigated the ability of PMN to secrete interleukin-6 (IL-6), a molecule known to be involved in inflammatory reactions. Using RNA blotting analysis and bioassays, we show that PMN could be induced to synthesize transcripts specific for IL-6, indistinguishable in size from IL-6 mRNA produced by activated human macrophages. Consequently, PMN released IL-6-like activity into their culture supernatants that could be neutralized by monospecific anti-IL-6 antibody. Interleukin-6 secretion by PMN, however, required previous stimulation with GM-CSF or tumor necrosis factor-alpha (TNF-alpha), whereas other cytokines, including interleukin-3 (IL-3), granulocyte-CSF (G-CSF), macrophage-CSF (M-CSF), interferon gamma (IFN-gamma), and lymphotoxin (LT), failed to induce IL-6 mRNA accumulation and protein secretion by PMN. Similar to GM-CSF and TNF-alpha, other compounds, including the inhibitor of protein synthesis cyclohexemide (CHX), endotoxin (Escherichia coli-derived lipopolysaccharide), and phorbol myristate acetate (PMA) (but not the chemoattractant N-formyl-methionyl-leucyl-phenylalanine [FMLP]), induced detectable levels of IL-6 transcripts in PMN.
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PMID:Inducible production of interleukin-6 by human polymorphonuclear neutrophils: role of granulocyte-macrophage colony-stimulating factor and tumor necrosis factor-alpha. 169 93

Superoxide anion (O2-) generation by human blood neutrophils induced by phorbol myristate acetate, formyl-methionyl-leucyl-phenylalanine, and monoclonal antibody YI51 was measured 24 h after incubation in medium alone, medium with recombinant human granulocyte colony-stimulating factor (rG-CSF), and medium with lipopolysaccharide (LPS). Monoclonal antibody YI51 was able to bind to neutrophils and induce O2- generation after the addition of anti-mouse immunoglobulin antibody as a cross-linking agent. In the 24-h culture, there was no significant difference in neutrophil survival among the three cultures. The amount of O2- generated by neutrophils in control medium markedly decreased compared with that before culture. However, cells in medium with rG-CSF or LPS maintained the ability to generate O2- well or moderately, respectively. Thus, the activity maintained by rG-CSF and LPS was neutralized by the anti-G-CSF serum. Furthermore, significant amounts of G-CSF were detected in supernatants of neutrophils cultured with LPS for 24 h. It was not detectable, however, in control supernatants. To examine whether the phenotype of the plasma membrane of cells changed in the 24-h culture, expression of CD16 (FcR III) and YI51 antigens was analyzed by flow cytometry. The expression of CD16 and YI51 antigens on cells cultured with rG-CSF or LPS was maintained compared with that of control cells. These observations thus indicate that G-CSF is one of the factors essential to maintain the functioning and phenotype of mature neutrophils.
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PMID:Recombinant granulocyte colony-stimulating factor and lipopolysaccharide maintain the phenotype of and superoxide anion generation by neutrophils. 169 8

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 previously shown that the antiviral state of explanted mouse peritoneal macrophages (PM) decays during in vitro culture and that this decay is much more rapid in Lpsd PM than it is in Lpsn PM. Moreover, Lpsn PM can transfer the antiviral state to other cells, whereas Lpsd PM cannot. In vitro treatment of Lpsn PM with different agents [i.e., bacterial lipopolysaccharide (LPS), interferon (IFN)-gamma, tumour necrosis factor (TNF)-alpha, macrophage colony-stimulating factor (M-CSF) and antibody to Mac-1 antigen] induced an antiviral state to vesicular stomatitis virus (VSV) which was inhibited by antibodies to IFN-beta. Treatment of Lpsn PM with LPS or IFN-gamma resulted in greater accumulation of IFN-beta mRNA, whereas no change in the barely detectable levels of IFN-alpha mRNA was observed. Marked accumulation of IFN-beta mRNA was also observed in PM after TNF-alpha treatment. M-CSF and IFN-gamma (but not LPS) also induced an IFN-mediated antiviral state in Lpsd PM. Low levels of spontaneous transcription of IFN-beta mRNA were detected in nuclei from Lpsd PM. Treatment of Lpsd PM with IFN-gamma for 3 h resulted in the accumulation of IFN-beta mRNA without any concomitant increase in the transcription of the IFN-beta gene, as determined by run-on transcription assays with isolated nuclei. The addition of as little as I international unit/ml of IFN-gamma to PM resulted in a 100-fold inhibition of VSV yield. As antibodies to IFN-alpha/beta inhibited only a portion of the IFN-gamma-induced antiviral state, such an antiviral state might reflect the synergism between IFN-gamma and endogenous IFN-beta. In fact, the addition of low doses of both IFN-gamma and IFN-beta to either Lpsn or Lpsd PM resulted in synergistic antiviral effects. In vivo treatment of Lpsd mice with granulocyte-macrophage (GM)-CSF, M-CSF, IFN-gamma or Newcastle disease virus rendered peritoneal cells capable of transferring an antiviral state. These results indicate that (i) various stimuli can induce IFN-beta production by PM, (ii) Lpsd PM spontaneously transcribe low levels of IFN-beta mRNA, even though they cannot transfer an antiviral state, (iii) different stimuli, but not LPS, induce a normal IFN response in Lpsd PM, (iv) IFN-gamma increases the accumulation of IFN-beta mRNA in Lpsd PM by post-transcriptional mechanisms and (v) IFN-gamma may act synergistically with endogenous IFN-beta in inducing a potent antiviral state to VSV in PM.
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PMID:Effects of different biological response modifiers on interferon expression in bacterial lipopolysaccharide (LPS)-responsive and LPS-hyporesponsive mouse peritoneal macrophages. 170 75

This study sought to determine whether endogenous tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and granulocyte-colony-stimulating factor (G-CSF) were detectable in sera of lipopolysaccharide (LPS)-treated cancer patients. Twenty patients received an intravenous bolus of purified LPS from Salmonella abortus-equi (4.0 ng/kg). Patients were pretreated with ibuprofen (1,600 mg) to prevent constitutional side effects like fever and chills. Serum TNF-alpha levels increased from less than 0.01 ng/ml before treatment up to maximal levels of 21 ng/ml, peaking 1.5 h after LPS injection. Similarly, serum IL-6 concentrations increased from less than 0.01 to 11 ng/ml, but peak levels were obtained 30 min later than TNF-alpha. Circulating G-CSF appeared still later than TNF-alpha and IL-6. It was detectable within 3 h and peaked 6 h after LPS injection. Parallel to the release of the above cytokines a marked increase in granulocyte counts was observed. In all patients administration of LPS led to an acute-phase response as measured by C-reactive protein.
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PMID:Treatment of cancer patients with endotoxin induces release of endogenous cytokines. 171 15

Triggering of the CD3 molecule by in vivo injection of the hamster anti-murine CD3 monoclonal antibody 145-2C11 in adult BALB/c mice leads to massive although transient T cell activation. High levels of tumour necrosis factor (TNF), interferon-gamma (IFN-gamma), IL-2, IL-3 and IL-6 are released into the circulation 1 to 8 h after a single 10 micrograms 145-2C11 i.v. injection. This release induces an impressive self-limited physical reaction associating hypothermia, hypomotility (as assessed by actimetry), diarrhoea, piloerection and even death when high doses (a single dose of greater than 100 micrograms/mouse injection) are administered. In vivo injection of 145-2C11 to other selected mouse strains, namely NZW, CBA/J and C3H/HeJ, induced both different cytokine release patterns and sickness. 145-2C11 induced significant release of TNF and IL-2 in all four strains. At variance, IFN-gamma was only detected in BALB/c mice sera which, in terms of physical reaction (hypothermia and hypomotility) were the most affected. Higher and long-lasting circulating IL-3/GM-CSF levels were present in CBA/J sera, correlating with a later recovery. These results underline heterogeneity in the in vivo cell activation pattern among different mouse strains, when triggering T lymphocytes via the CD3/Ti molecule as compared to exclusive targeting of monocyte/macrophages by means of lipopolysaccharide.
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PMID:Inter-mouse strain differences in the in vivo anti-CD3 induced cytokine release. 172 Oct 15


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