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)

It has previously been shown that interleukin-1 (IL-1) directly stimulates the release of CRH-41 from rat hypothalamus in vitro, suggesting that cytokines may mediate the effects of changes in immune state on the hypothalamo-pituitary adrenal axis (HPA). However, it is likely that several cytokines can cause changes in neuroendocrine function, and we have now investigated a series of others for central activity on the HPA: IL-2, IL-6, IL-8, tumor necrosis factor (cachectin), interferon-alpha 2, and interferon-gamma. The static rat hypothalamic incubation system used involves fresh hypothalamic explants with consecutive 20-min incubation, and estimation of CRH-41 concentrations in the medium by a specific RIA; the acute effects of cytokines on ACTH release from rat dispersed pituitary cells were also measured. IL-6 increased hypothalamic CRH-41 secretion in the range 10-100 U/ml, but had no effect on isolated median eminences incubated in vitro under the same conditions. IL-6 (1-1000 U/ml) also had no effect on the secretion of ACTH from freshly dispersed rat anterior pituitary cells when administered in 10-min pulses. The effects of both IL-1 and IL-6 were antagonized by blockade of the eicosanoid cyclooxygenase pathway, but not by lipooxygenase blockade. Neither IL-2 (1-10000 U/ml), IL-8 (0.1-10 nM), tumor necrosis factor (10-1000 U/ml), interferon-alpha 2 (10-1000 U/ml) nor interferon-gamma (10-1000 U/ml) had any effect on hypothalamic CRH-41 release or pituitary ACTH release. It is therefore concluded that IL-6, like IL-1, can exert a potent enhancing effect on the HPA by acutely stimulating the secretion of CRH-41 from the hypothalamus at a site above the level of the median eminence, at concentrations known to occur in human plasma and cerebrospinal fluid. These effects are probably mediated by cyclooxygenase products. Acute stimulatory effects of the other cytokines investigated on the HPA are unlikely to be exerted through changes in either CRH-41 or ACTH directly.
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PMID:Interleukins-1 and -6 stimulate the release of corticotropin-releasing hormone-41 from rat hypothalamus in vitro via the eicosanoid cyclooxygenase pathway. 184 5

Interleukin-8 (IL-8), formerly known as NAP-1, is formed by a variety of cells upon stimulation with IL-1 or tumor necrosis factor (TNF). The biologic activity of the cytokine involves activation of almost every neutrophil function studied so far in different species. In the present study, we compared the effects of recombinant human IL-8 (rIL-8) and the lipid mediators, leukotriene B4 (LTB4) and platelet-activating factor (PAF), on neutrophil functions in dogs. All three chemotactic factors induced neutrophil aggregation and chemotaxis, with rIL-8 being far more potent than LTB4 and PAF. The migration induced by rIL-8 was significantly greater than that observed towards LTB4 and PAF. In the aggregation assay, rIL-8 was shown for the first time to be a potent stimulant. The aggregation response was more persistent than that obtained with LTB4 and PAF and the potency of rIL-8 was greater. An intradermal dose-response study showed that rIL-8 is an extremely potent inducer of selective neutrophil infiltration in canine skin. The infiltration was more pronounced than following injection of LTB4 or PAF. It was proposed that the superior effect of rIL-8 was caused by a synergistic effect between injected rIL-8 and LTB4, which was shown to be produced in biologically active amounts by canine neutrophils stimulated with rIL-8. From a therapeutic point of view, the simultaneous presence of rIL-8 and LTB4 in inflammatory skin diseases highlights the need to develop drugs that inhibit the production and/or effect of both mediators.
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PMID:Recombinant human interleukin-8 is a potent activator of canine neutrophil aggregation, migration, and leukotriene B4 biosynthesis. 184 1

Interleukin-8 (IL-8) is a newly described leukocyte chemotactic and activating cytokine that belongs to the novel family of inflammatory cytokines whose genes locate on human chromosome 4, q12-21 region. The production of IL-8 is usually not constitutive and can be induced rapidly and abundantly in different cell types by a variety of stimuli such as lipopolysaccharide, interleukin-1, tumor necrosis factor-alpha as well as a tumor promotor phorbol myristate acetate. We report here that in addition to these stimuli the IL-8 gene can also be induced by the protein X of the hepatitis B virus (HBV-X) as evidenced by the enhanced IL-8 mRNA expression and IL-8 production observed in HBV-X-transfected cells. Furthermore, using several deletion mutants of the 5'-flanking regulatory region of the human IL-8 gene linked to the chloramphenicol acetyl transferase gene as a reporter, we have established here that both nuclear factor kB and CCAAT/enhancer-binding protein-like cis-elements located at -94 to -71 base pairs of IL-8 gene are essential and sufficient for the induction of the IL-8 gene by HBV-X. The same elements have been identified recently by us to be interleukin-1-, tumor necrosis factor-alpha-, and phorbol myristate acetate-responsive elements on the IL-8 gene. This suggests the existence of a common pathway for these inflammatory cytokines and HBV-X to activate the IL-8 gene. These observations might be relevant to the pathogenesis of inflammation in viral hepatitis.
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PMID:Hepatitis B virus X protein transactivates human interleukin-8 gene through acting on nuclear factor kB and CCAAT/enhancer-binding protein-like cis-elements. 185 9

Production of the neutrophil-activating peptide (NAP)-1/IL-8 by mononuclear phagocytes from patients with RA and from control subjects was studied under various conditions. Mononuclear cells from bone marrow (BMMC), PBMC, and synovial fluid (SFMC) were cultured for up to 48 h in the absence or presence of Escherichia coli LPS, different interleukins, interferon-gamma, zymosan, or immune complexes, and the neutrophil-stimulating activity released into the culture medium was determined. As shown by neutralization with an antiserum raised against human recombinant NAP-1/IL-8, over 90% of this activity could be attributed to NAP-1/IL-8. In unstimulated mononuclear cells from control individuals and BMMC from RA patients, the production of NAP-1/IL-8 was very low and was enhanced moderately by stimulation with LPS. By contrast, the spontaneous production of NAP-1/IL-8 was 3- to 10-fold higher in PBMC and even much higher in SFMC from RA patients. In all instances, the yield of NAP-1/IL-8 could be enhanced by stimulation in culture. In addition to LPS, rheumatoid factor-containing immune complexes, zymosan, and IL-1 were highly effective in inducing NAP-1/IL-8 production, while IL-3, GM-CSF, tumor necrosis factor (TNF), and IL-2 were somewhat less potent. An inhibitory effect was obtained with IFN-gamma, which significantly decreased the spontaneous NAP-1/IL-8 release from SFMC and the IL-1- and LPS-induced NAP-1/IL-8 from RA and control PBMC. Inhibition was also observed with glucocorticoids. The production of NAP-1/IL-8 was markedly reduced by dexamethasone in phagocytosis-stimulated PBMC, and almost totally inhibited in SFMC obtained from joints after intraarticular administration of betamethasone. By contrast, the cyclooxygenase inhibitor, indomethacin, tended to increase the NAP-1/IL-8 yield from PBMC in culture.
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PMID:Enhanced production of neutrophil-activating peptide-1/interleukin-8 in rheumatoid arthritis. 189 27

A hyperdynamic sepsis model was set up in seven adult baboons to evaluate neutrophil-activating peptide-1/interleukin (IL)-8 (NAP-1/IL-8), IL-1 beta, IL-6, tumor necrosis factor-alpha (TNF alpha), and IFN-gamma in plasma. By continuous intravenous administration of 10(10) cfu/kg live Escherichia coli over 8 h with additional infusion therapy (less than or equal to 50 ml/kg/h), endotoxin plasma levels of 2.7-22.3 ng/ml were observed. In plasma the kinetics of NAP-1/IL-8 and IL-6 were similar to those of IL-1 at the end of the experiment (8 h) (peak median values, 34, 4197, and 230 ng/ml, respectively). Differences were greatest for IL-6. Monocyte activation during sepsis was confirmed by elevated plasma neopterin levels (91-139 mumol/mmol of creatine). Granulocyte activation was evident from both incipient neutropenia and the massive release of neutrophil elastase into the plasma as measured by a new immunoassay (peak level, 374 ng/ml). Thus, in primate bacteremia, early TNF release is followed by a concomitant increase of NAP-1/IL-8 with plasma kinetics similar to those of IL-6 and IL-1 and accompanied by massive activation of neutrophils.
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PMID:Plasma neutrophil-activating peptide-1/interleukin-8 and neutrophil elastase in a primate bacteremia model. 190 12

Apart from lymphocytes, mononuclear phagocytes play an essential role as target cells for human immunodeficiency virus (HIV). Circulating blood monocytes (MOs) and tissue macrophages (M phi) may harbor and distribute the virus throughout the body. In addition, proinflammatory monokines [interleukin-1 (IL-1), IL-6, IL-8, tumor necrosis factor-alpha (TNF-alpha)] may contribute to the pathogenesis of HIV-mediated diseases. We have established a culture system on hydrophobic Teflon membranes for blood-borne MOs/M phi. Both freshly isolated MOs as well as MO-derived M phi could be infected with a monocytotropic HIV-1 isolate (HIV-1D117III) derived from a perinatally infected child. The virus production monitored by assay for viral antigen in cell-free supernatant is continuous for several weeks. We analyzed the stimulus response and the secretory repertoire of MOs/M phi early after infection with HIV as well as in long-term cultured, virus-replicating cells. Infected MOs/M phi respond to interferon-gamma more effectively than control cells as estimated from the release of neopterin. The response to lipopolysaccharide was regulated differently: whereas the proinflammatory cytokines IL-1, IL-6, IL-8 and TNF-alpha were up-regulated and even constitutively secreted upon infection, the production of the hematopoietin macrophage-colony-stimulating factor decreased. High levels of TNF-alpha and IL-1 might augment the infectibility of M phi by HIV in an autocrine manner. Our results may provide some explanation for the immunologic dysfunction, the hematopoietic failure and the chronic inflammatory disease occurring in HIV-infected patients.
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PMID:Secretory repertoire of HIV-infected human monocytes/macrophages. 190 44

The pulmonary fibroblast's (PF) unique location allows it to communicate in a bidirectional fashion between the vascular compartment and alveolar airspace, placing it in a strategic position for the elicitation of inflammatory leukocytes into the lung. In this study, we demonstrate that PF may contribute to pulmonary inflammation through the production of a potent neutrophil chemotactic factor, interleukin (IL)-8. PF-derived IL-8 expression was dependent upon stimulation by either tumor necrosis factor (TNF) or IL-1 but not lipopolysaccharide (LPS). Both TNF and IL-1 stimulation of PF resulted in a time- and dose-dependent expression of steady-state levels of mRNA, antigen, and specific chemotactic activity consistent with IL-8. Because it was apparent that cytokine networking may exist in the lung between alveolar macrophage (AM)-derived cytokines and the production of PF-derived IL-8, we next examined an in vitro model of cellular communication within the lung. We determined that LPS-stimulated AM-conditioned media induced significant levels of PF-derived IL-8 mRNA, which was inhibited by preincubation with specific neutralizing TNF and IL-1 beta antibodies. Furthermore, when AM were directly co-cultured with PF and stimulated with LPS, the kinetic analysis of PF-derived antigenic expression of IL-8 was shifted toward the right. This suggested that PF-derived IL-8 expression in co-culture was first dependent upon activation of the AM by LPS and subsequent elaboration of macrophage inflammatory mediators. These data provide evidence that cytokine networking between AM and PF may be operative in the lung, culminating in the generation of IL-8 and elicitation of inflammatory leukocytes.
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PMID:Pulmonary fibroblast expression of interleukin-8: a model for alveolar macrophage-derived cytokine networking. 193 Oct 78

The human alveolar macrophage (AM) is an important immune effector cell of the lung, as this cell possesses potent antimicrobial activities and has the ability to present antigen. In addition, the Am can secrete a number of regulatory and chemotactic cytokines in response to both endogenous and exogenous stimuli. In this study, we demonstrate that the adherence of AM to plastic or cellular substrates is an important activation event leading to the gene expression of novel chemotactic cytokine interleukin (IL)-8. The culturing of AM on plastic induced the time-dependent accumulation of IL-8 mRNA. In addition, adherence of these cells induced the gene expression of the proinflammatory cytokines tumor necrosis factor-alpha and IL-1 beta. This adherence phenomenon was not specific to plastic, as AM cultured on collagen- or fibronectin-coated plates also expressed IL-8 mRNA upon adherence. The adherence of Am resulted in the induction of de novo IL-8 mRNA synthesis, as this mRNA accumulation was completely abrogated by actinomycin D. Adherence-induced IL-8 mRNA expression was not altered by cycloheximide, suggesting that de novo or ongoing protein synthesis was not required for induction of IL-8 message. Adherence of AM to plastic not only upregulated IL-8 mRNA levels but also induced the production of extracellular IL-8 immunoreactive protein. Both adherent and nonadherent AM treated with lipopolysaccharide generated substantial amounts of IL-8 mRNA. Adherence and lipopolysaccharide, however, acted in a synergistic fashion to dramatically augment the production of extracellular IL-8 from these cells. Our findings would suggest that AM adherence is an important macrophage-activating event that may play a critical role in the modulation of lung inflammatory responses.
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PMID:Interleukin-8 gene expression from human alveolar macrophages: the role of adherence. 195 85

Human epidermal keratinocytes constitutively produce a variety of cytokines, including neutrophil chemotactic peptide named epidermal cell-derived thymocyte-activating factor, which has been later confirmed to be interleukin 1 (IL-1). Because recombinant IL-1 lacks chemotactic activity, in the present study, we examined the exact nature of the neutrophil chemotactic peptide in the culture supernatant of normal human epidermal keratinocytes. Normal human epidermal keratinocytes produced a neutrophil chemotactic factor, which was also chemotactic for T lymphocytes. Molecular sieve chromatography revealed an approximate molecular size of 11,000 daltons. The activity was retained after heating at 100 degrees C for 10 min, and at a pH between 4 and 11, but was partially inactivated at pH 3, or by trypsin treatment. The chemotactic activity was not inhibited by the treatment with anti-IL-1 antibody. Its production by keratinocytes was stimulated by IL-1 and lipopolysaccharide but not by UV irradiation, tumor necrosis factor-alpha or by interferon-gamma. The neutrophil chemotactic activity in vivo was confirmed by the intradermal injection of the factor into guinea pigs. Blocking study with monoclonal antibodies against NAP-1/IL-8 confirmed that the neutrophil chemotactic factor is IL-8.
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PMID:Normal human epidermal keratinocyte-derived neutrophil chemotactic factor. 207 75

The protein-bound polysaccharide extracted from a fungus, PSK, has been used as a biological response modifier in the treatment of cancer patients in Japan for over ten years. Although the antitumor mechanism of PSK is not fully understood, host-mediated antitumor activity has been claimed to play a significant role. The administration of PSK to tumor-bearing rodents inhibited tumor growth and modulated immune responses. To clarify the potential immunomodulating activities of PSK, we examined the direct effect of PSK on cytokine gene expression and production in human peripheral blood mononuclear cells (PBMC) in vitro. As determined by Northern blotting, PSK was a potent inducer of gene expression for IL-1 alpha, IL-1 beta, IL-6, IL-8, tumor necrosis factor (TNF-alpha) and monocyte chemotactic and activating factor (MCAF), but not for IL-2 and lymphotoxin (LT). Expression of mRNA occurred at 1-3 hr in a dose dependent manner using from 5-400 micrograms/ml of PSK. Furthermore, these cytokines were also produced in response to PSK as detected by ELISA, RIA or bioassays. We speculate that these cytokines may mediate immunoenhancing actions of PSK in vivo.
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PMID:Induction of gene expression and production of immunomodulating cytokines by PSK in human peripheral blood mononuclear cells. 209 Aug 74


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