Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10145 (IL-8)
 23,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In response to bacterial cell wall products such as LPS, monocytes produce IL-8, a powerful neutrophil chemotaxin. However, in the absence of bacterial pathogens, immune complex-mediated diseases such as rheumatoid arthritis are associated with high levels of IL-8 in monocyte-rich compartments. Since it is known that IgG-containing immune complexes can recruit neutrophils via an Fc gamma R-dependent process, we hypothesized that cross-linking of monocyte Fc gamma receptors may induce IL-8. To test this hypothesis, peripheral blood mononuclear cells were evaluated for IL-8 induction in response to immobilized LPS-free pooled human IgG. Immobilized IgG, but not soluble IgG, induced IL-8 in a dose-dependent manner (p < 0.05, r = 0.99). This induction corresponded with an up-regulation in IL-8 steady state mRNA levels that peaked at 4 h. The released IL-8 was functional, since supernatants induced concentration-dependent neutrophil migration that was inhibited by a monoclonal anti-IL-8 Ab. Evaluation of purified monocytes for IL-8 production, as well as FACS analysis of IgG-stimulated PBMC preparations, demonstrated that monocytes are the principal IL-8 producer cell. Thus, monocyte Fc gamma R cross-linking induces biologically active IL-8, which may participate in the pathogenesis of immune complex-mediated diseases.
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PMID:Monocyte Fc gamma receptor cross-linking induces IL-8 production. 767 29

CD14 has been reported to function as a receptor for bacterial LPS complexed with serum proteins, transducing an activation signal for TNF-alpha production. We found that the anti-CD14 mAb MEM-18 inhibited not only LPS-induced release of TNF-alpha, but also LPS-induced, TNF-alpha independent release of IL-6 and IL-8 by human monocytes and alveolar macrophages. Inhibitory effect of MEM-18 was detected both in the presence of human or bovine calf serum and under serum-free conditions. In contrast, MEM-18 did not block release of these cytokines induced by IL-1 beta, TNF-alpha, PMA, and zymosan. We conclude that CD14 is involved in LPS-induced release of TNF-alpha, IL-6, and IL-8 by monocytes and alveolar macrophages and that this receptor appears to be able to recognize LPS directly in the absence of serum.
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PMID:Involvement of CD14 in lipopolysaccharide-induced tumor necrosis factor-alpha, IL-6 and IL-8 release by human monocytes and alveolar macrophages. 768 Oct 82

Recent work has established that bacterial endotoxin (LPS) binds to the plasma protein LPS-binding protein (LBP) forming high affinity complexes (LPS-LBP), that LBP is an opsonin for LPS-bearing particles, and that LPS-LBP complexes are potent agonists for monocytic cells (MO). mAb to the MO plasma membrane protein, CD14, inhibit LBP-dependent binding of LPS to MO, and LPS-LBP-dependent stimulation of cytokine release from MO. These data suggest that CD14 functions as a membrane receptor for LPS but do not demonstrate a direct association of LPS with CD14. Calcitriol was used to induce a high level of CD14 expression in the human monocyte-like cell line THP-1, resulting in enhanced responses of these cells to LPS-LBP complexes manifested by enhanced binding of LPS and a decrease in the amount of LPS needed to induce IL-8 release. An Re595 LPS derivative containing a radioiodinated, photoreactive, phenyl azide (125I-ASD-LPS) was used in cross-linking experiments to identify membrane proteins in calcitriol-treated THP-1 cells that interact with LPS. 125I-ASD-LPS was added to calcitriol-induced THP-1 cells in the presence or absence of LBP, the mixture photolyzed, and the resultant radioiodinated proteins analyzed by SDS-PAGE and autoradiography. We observed strong cross-linking of 125I-ASD-LPS to a 55-kDa membrane protein when LBP was present, but failed to observe radiolabeling of any other proteins with apparent molecular masses distinct from CD14. The cross-linked product was identified as CD14 by immunoprecipitation with anti-human CD14 mAb. Studies with human CD14 expressing transfectants of the murine B cell line 70Z/3 also revealed LBP-dependent cross-linking of 125I-ASD-LPS to CD14. These data document binding of LPS to a specific membrane protein that serves as an LPS receptor.
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PMID:Cross-linking of lipopolysaccharide (LPS) to CD14 on THP-1 cells mediated by LPS-binding protein. 768 Oct 85

We studied the effect of a 4-hr preexposure to LPS on the ability of human monocytes to respond to a subsequent stimulation with LPS in terms of cytokine production. LPS-preexposed monocytes did not produce TNF on LPS restimulation, but they retained the ability to produce IL-1 beta, IL-6, and IL-8. LPS-tolerant monocytes were still capable of producing TNF when restimulated with zymosan. Down-regulation of TNF by LPS tolerance was also evident at the mRNA level. To investigate the possible mechanisms underlying this phenomenon, we also studied the effect of LPS preexposure on membrane CD14, which was suggested to be an LPS receptor, and on intracellular cAMP, an inhibitor of TNF production. LPS induced a 50% decrease in CD14 expression. On the other hand, the increase in cAMP levels by LPS was not affected by preexposure to LPS. In conclusion, (a) TNF is more rapidly down-regulated than IL-1 beta, IL-6, and IL-8 during LPS tolerance in vitro; (b) early LPS tolerance is associated with decreased CD14, which might partially explain the decreased LPS response; and (c) a feedback mechanism controlling TNF synthesis, cAMP elevation, is not down-regulated in LPS tolerance.
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PMID:Early down-regulation of TNF production by LPS tolerance in human monocytes: comparison with IL-1 beta, IL-6, and IL-8. 769 88

In vitro, IL-10 inhibits T cell proliferation and LPS-induced monocyte production of IL-1, TNF-alpha, IL-6, and IL-8. We studied the safety and immunomodulatory effects of IL-10 administration in humans. Seventeen healthy volunteers received a single i.v. bolus injection of either human IL-10 (1, 10, or 25 micrograms/kg) or placebo. Routine safety parameters, lymphocyte phenotypes, T cell proliferative responses, and stimulus-induced cytokine production were assessed before and 3, 6, 24, and 48 h after injection. There were no adverse symptoms or signs after IL-10 administration. A transient neutrophilia and monocytosis that peaked at 6 h (45-160% above base line) was observed. However, lymphocyte counts fell by 25% 3 and 6 h after the injection (p < 0.01). In particular, lymphocytes expressing the T cell surface markers CD2, CD3, CD4, CD7, and CD8 were significantly decreased. Mitogen-induced T cell proliferation was suppressed by up to 50% (p < 0.01) in the two higher dose groups. Significant dose-dependent inhibition (65-95%) of TNF-alpha and IL-1 beta production from whole blood stimulated ex vivo with endotoxin occurred after each dose of IL-10. In contrast, there was no reduction in the production of their respective antagonists, TNF soluble receptor p55 or IL-1 receptor antagonist. We conclude that a single intravenous injection of IL-10 is safe in humans, has inhibitory effects on T cells, and suppresses production of the pro-inflammatory cytokines TNF-alpha and IL-1 beta.
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PMID:A randomized, controlled trial of IL-10 in humans. Inhibition of inflammatory cytokine production and immune responses. 773 Jun 51

Interleukin-8 (IL-8) is a chemoattractant cytokine for polymorphonuclear neutrophils, and is found at the site of inflammation and infection. The levels of IL-8 from an elderly (ages 65-79) and young (ages 20-27) population were compared. Secretion of IL-8 was measured in monocyte conditioned medium (MCM), under both a spontaneous condition and with stimulation with detoxified LPS (10 mg/ml). Spontaneous production of IL-8 in the elderly group (39.4 +/- 8.3 ng/ml, n = 16) was found to be significantly lower than the control group (66.4 +/- 5.0 ng/ml, n = 17), P < 0.01. A sex difference was observed within the elderly population, with the male elderly producing 8.8 +/- 2.1 ng/ml of IL-8 and the elderly females producing levels of 57.8 +/- 9.1 ng/ml. There was a good correlation between IL-8 and IL-1 production in the elderly but differences between the elderly and young production of IL-1 did not reach statistical significance. IL-8 and TNF production did not correlate. Upon stimulation with the LPS, the male elderly levels increased eightfold (70.1 +/- 11.8 ng/ml) and was significantly different from the young male level, P < 0.01, while the female elderly showed no change with stimulation. No sex difference was observed in the control population. These results indicate that the spontaneous secretion of IL-8 in elderly males is lower than that of both elderly females and the young control group. However, upon stimulation with LPS, the elderly males are capable of an overproduction of IL-8 when compared to the young group and the elderly females. This overproduction may be the result of an in vivo priming in this healthy elderly group. The female elderly followed a pattern similar to the young group, showing no change upon stimulation with the detoxified LPS. Sex differences related to the immune system have been noted in the past with females having a more active immune system, and these results may be related to this difference.
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PMID:Cytokine production and aging: overproduction of IL-8 in elderly males in response to lipopolysaccharide. 774 91

A newly synthesized demethylpodophyllotoxin derivative, 4-O-butanoyl-4'-demethylpodophyllotoxin (BDPT) or BN58705, has recently been shown to exert a potent cytotoxic activity in vitro against a variety of drug-resistant human tumor cell lines. The effect of this agent on effector cells of the immune system, however, has not been examined. The present study investigated the effect of BDPT on the response of activated human peripheral blood derived monocytes (PBM) to secrete cytokines. Activation of PBM overnight with LPS, IFN-gamma, or PMA resulted in secretion into the supernatant of TNF-alpha, IL-1 beta, IL-6, and IL-8 as assessed by ELISA. The addition of BDPT to the stimulated cultures resulted in significant inhibition of TNF-alpha and IL-1 beta secretion, whereas the secretion of IL-6 and IL-8 was not affected. The selective inhibition of TNF-alpha and IL-1 beta secretion by BDPT-treated PBM was observed with all three stimuli tested. The inhibitory effect mediated by BDPT was concentration dependent and was optimal at 6-20 microM. Time kinetic analysis indicated that the inhibition of secretion was rapid and detected as soon as 2 hr following stimulation of the PBM and lasted for as long as 24 hr. A comparison was made between BDPT and pentoxyfilline, a xanthine-derived phosphodisterase inhibitor that was reported to inhibit TNF-alpha and IL-1 beta secretion by PBM. Both BDPT and PTX showed similar time kinetics and patterns of inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Inhibition of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) secretion but not IL-6 from activated human peripheral blood monocytes by a new synthetic demethylpodophyllotoxin derivative. 781 57

The present study was aimed at characterizing the effects of in vitro exposure to GM-CSF on blood monocytes and tumor-associated macrophages (TAM) in human ovarian cancer. Purified populations of TAM from ovarian cancer patients were studied in terms of expression of surface molecules, cytokine production and tumor cytotoxicity after overnight incubation with GM-CSF or IFN gamma and LPS, used as reference activators. GM-CSF augmented the surface expression of ICAM-I and CD18 in TAM and in blood monocytes. Stimulation was more prominent in monocytes than in TAM, which showed higher baseline expression of this adhesion molecule. ICAM-3 was not influenced by GM-CSF or by IFN gamma/LPS. GM-CSF-augmented ICAM-I expression was associated with higher levels of mRNA transcripts. The protein synthesis inhibitor cycloheximide super-induced basal and GM-CSF-induced ICAM-I transcripts, thus excluding a role for secondary polypeptide mediators. In the absence of stimuli, TAM produced higher levels, compared to monocytes, of IL-6 and IL-8 but not of IL-1 and TNF. GM-CSF augmented the production of IL-6 and IL-8 (but not that of IL-1 and TNF) in TAM, whereas it had little effect on blood monocyte. Tumoricidal activity was tested against two ovarian tumor cell lines (OVCAR3 and SW626). GM-CSF more prominently augmented monocyte cytotoxicity, while only 2 of 6 TAM preparations were stimulated by GM-CSF. These results suggest that GM-CSF selectively regulates the function of blood monocytes and TAM, the effect of this cytokine varying with the parameter and cell population examined. These data provide a rational and biological endpoint for further studies with GM-CSF as an activator of mononuclear phagocyte function in ovarian cancer.
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PMID:Effects of granulocyte-monocyte colony-stimulating factor (GM-CSF) on expression of adhesion molecules and production of cytokines in blood monocytes and ovarian cancer-associated macrophages. 782 34

Interleukin (IL)-10 is a potent immunosuppressant of monocyte/macrophage function and may help control the inflammatory response induced by bacterial infection. To analyze whether IL-10 is detectable in plasma of patients with septic shock and to evaluate its relationship with endotoxin (lipopolysaccharide [LPS])-induced and monocyte/macrophage-induced inflammatory response, plasma IL-10, tumor necrosis factor (TNF)-alpha, IL-1 beta, IL-6, IL-8, LPS, and neopterin were studied in 24 patients with septic shock and in 12 critically ill patients. Eighty-three percent of patients with septic shock and 25% of critically ill patients had detectable levels of IL-10 (P < .001). There was a significant correlation between plasma IL-10, neopterin (r = .72), TNF-alpha (r = .76), IL-6 (r = .68), and IL-8 (r = .61) levels in patients with septic shock. Monocyte/macrophage activation leads to massive secretion of IL-10, which, however, seems to be unable to control the increased production of proinflammatory mediators during septic shock.
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PMID:Interleukin-10 and the monocyte/macrophage-induced inflammatory response in septic shock. 756 Dec 9

HuGRO, IL-8 and gamma-IP-10 belong to a recently described superfamily of genes encoding a group of cytokines with inflammatory, growth regulating and/or leukocyte chemotactic properties (chemokines). We studied huGRO, IL-8 and gamma-IP-10 gene expression in unstimulated and stimulated (TNF alpha, INF gamma, TNF alpha + IFN gamma, IL-1 beta, PMA and LPS) normal human keratinocytes by Northern blot analysis. The mRNA for none of the three chemokines was detectable in unstimulated keratinocytes, but considerably elevated levels of huGRO and IL-8 mRNA, but not of gamma-IP-10 mRNA, were found in the presence of cycloheximide, indicating that huGRO and IL-8 mRNA, but not gamma-IP-10 mRNA, are constitutively produced. gamma-IP-10 mRNA was exclusively induced by IFN gamma, with a strong and transient rise between 8 and 18 h, and superinduced by the combination of IFN gamma and TNF alpha, indicating marked synergism. Both huGRO and IL-8 mRNA were induced by TNF alpha and PMA (a strong and transient rise between 2 and 8 h), but not by IFN gamma or LPS. The combination of TNF alpha and IFN gamma did not show a synergistic effect. In addition, IL-1 beta transiently upregulated huGRO mRNA but failed to induce IL-8 mRNA. Using specific oligonucleotides for alpha, beta and gamma huGRO, TNF alpha was found to induce all three forms, alpha and beta to an equal extent and gamma to a lesser extent.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Human growth factor (huGRO), interleukin-8 (IL-8) and interferon-gamma-inducible protein (gamma-IP-10) gene expression in cultured normal human keratinocytes. 786 61


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