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)

Expression of lymphokine genes in the human astroglial cell lineage was studied. Primers for 9 different human lymphokines, from IL-1 alpha to IL-8, were used to analyze RNA transcripts in 5 cultured human astrocytoma cell lines and fresh brain specimens by PCR. mRNA transcripts for IL-8 were detected in all neuroglial cells. In addition to the cultured cells, we examined IL-8 gene expression within human malignant astrocytoma, peritumoral brain and autopsied normal brains. The result shows that tumor and cells of the surrounding reactive lesion express IL-8 genes, but it is not expressed in normal brains. Next, the concentration of IL-8 in supernatants of cultured cells was measured quantitatively by a solid phase ELISA assay. IL-8 activity was produced constitutively in all astrocytomas and increased markedly upon stimulation with IL-1 beta or TNF alpha, in both a time- and dose-dependent fashion. From these results, it is suspected that astroglial cell-derived IL-8 may take part in neutrophil-mediated inflammation which accompanies infection, degeneration and malignancy in the brain.
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PMID:Neoplastic and reactive human astrocytes express interleukin-8 gene. 140 9

In the present studies, the mechanisms underlying the inhibitory actions of lipocortin-1 on the pyrogenic and thermogenic properties of cytokines were investigated. Central (icv) injection of corticotropin-releasing factor (CRF, 4.7 micrograms) or the recombinant cytokines interleukin (IL)-1 alpha (50 ng), IL-1 beta (5 ng), IL-6 (20 ng), IL-8 (20 ng), or tumor necrosis factor-alpha (TNF-alpha, 1 microgram) in conscious rats produced significant increases in resting oxygen consumption (VO2, 13-26%) and colonic temperature (0.7-1.6 degrees C) within 2 h postinjection. Administration (icv) of a recombinant fragment (NH2-terminus, 1-188 amino acids) of human lipocortin-1 (1.2 micrograms) produced small increases in VO2 (< 5%) and body temperature (< 0.3 degrees C). Pretreatment (-5 min) with lipocortin-1 significantly attenuated the thermogenic and pyrogenic effects of centrally injected IL-1 beta (80% inhibition), IL-6 (60%), IL-8 (80%), or CRF (60%). However, pretreatment with lipocortin-1 failed to modify the actions of IL-1 alpha or TNF-alpha. We have previously demonstrated that the pyrogenic and thermogenic effects of IL-1 beta, IL-6, and IL-8 are dependent on the central actions of CRF, whereas IL-1 alpha and TNF-alpha act independently of CRF. Fever and thermogenesis induced by all of these cytokines (with the exception of IL-8) can also be prevented by administration of a cyclooxygenase inhibitor. The data presented here suggest that the potent antipyretic effects of lipocortin-1 may result from inhibition of the release or actions of CRF rather than modulation of eicosanoid synthesis.
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PMID:Inhibition of central actions of cytokines on fever and thermogenesis by lipocortin-1 involves CRF. 141 82

Neutrophil-activating peptide-1/interleukin-8 (NAP-1/IL-8) is a cytokine synthesized by various cell types. In the immune system NAP-1/IL-8 is part of an immune cascade initiated by IL-1 production. NAP-1/IL-8 affects hypothalamic function and its production is suppressed by steroids. Therefore, it might be expected that NAP-1/IL-8 would be produced in brain areas involved in the control of the hypothalamic-pituitary-adrenocortical axis (HPA). NAP-1/IL-8 mRNA was localized by in situ hybridization in the paraventricular nucleus of the hypothalamus and hippocampus. Those areas also express the genes encoding interleukin-1-alpha (IL-1 alpha), IL-1 beta, IL-1 receptors, and IL-1 receptor antagonist (IL-1ra). This suggests that an immune cascade, which is well characterized in the immune system, may exist in brain, in areas of relevance to the regulation of stress-related neuroendocrine function.
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PMID:Neutrophil-activating peptide-1/interleukin-8 mRNA is localized in rat hypothalamus and hippocampus. 142 Nov 31

As a preliminary to transducing human melanoma cells with lymphokine genes, we sought for constitutive gene expression and production of eight interleukins, tumour necrosis factors and granulocyte-colony stimulating factor in 19 human melanoma cell lines. Conversion of RNA into cDNA by reverse transcriptase and polymerase chain reaction (RT-PCR) were employed to evaluate gene expression while enzyme-linked immunosorbent assays (ELISA) or biological assays were used to assess the presence of proteins. No expression of interleukins (IL) 3, 4, and 5 or interferon-gamma RNA was found, while the other cytokines were variably expressed in melanoma lines, with IL-1 alpha, IL-1 beta, IL-6, IL-8, being detectable in most of the lines. At protein level, 10 melanoma cells were tested with ELISA and all were found to produce IL-8, five produced IL-6, two tumour necrosis factor (TNF)-alpha, one IL-1 alpha and two TNF beta. The levels of TNF beta were at the limit of test sensitivity. The amount of various cytokines released by the different lines varied widely. Biological assay with the D10-G4 clone confirmed the presence of IL-1 alpha in the supernatant of melanoma (ME) 10221 and revealed an IL-1 activity in the supernatant of Me 4024/1. The proliferating activity of melanoma supernatants on D10-G4 was inhibited by treatment with polyclonal antibodies against IL-1 alpha but not with antibodies against IL-1 beta. TNF biological activity was tested against the TNF-susceptible fibrosarcoma WEHI 164 clone 13.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Expression of cytokine genes, including IL-6, in human malignant melanoma cell lines. 145 Jun 72

Heart transplantation is now a viable therapeutic option for patients with certain end-stage cardiac diseases. However, episodes of rejection, opportunistic infection, and life-threatening side effects of generalized immunosuppression remain very real problems for these patients. A better understanding of the molecular mechanisms underlying rejection may provide the basis for the development of more specific, less toxic immunosuppressive therapies. While cytokines have long been implicated in the pathogenesis of rejection, the precise role of each cytokine in this process has yet to be defined. We report here the application of the polymerase chain reaction (PCR) to the detection of cytokine mRNA in biopsies obtained from heterotopic abdominal cardiac allografts in cynomolgus monkeys. With the exception of IL-6 and IL-8, cytokine transcripts were undetectable in samples obtained from the donor heart pretransplant. In contrast, IFN-gamma transcripts were detected in all transplants two days after surgery before evidence of rejection was demonstrable by histopathologic analysis. IL-1 beta, IL-2, and IL-6 transcripts were detected when minimal rejection was noted. At later times, IL-1 alpha, IL-1 beta, IL-2, IL-6, IL-8, TNF-beta, and IFN-gamma transcripts were detectable. Further characterization of the spectrum of cytokines expressed at various stages of rejection may lead to insights into the biology of transplant rejection and to the development of more specific and potent reagents to diagnose and/or treat rejection.
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PMID:Cytokine gene expression in rejecting cardiac allografts. 149 44

Synthesis of complement proteins and their regulation in resident cells of the central nervous system are important pathophysiologic factors that can affect the outcome of inflammatory central nervous system diseases. Primary cultures of rat astrocytes constitutively express C3 mRNA and produce C3 protein; both of them were enhanced by LPS or by a live as well as inactivated Newcastle disease virus, a neurotropic paramixovirus. TNF, IL-1 beta, and IL-8 also increased the levels of C3 mRNA and protein whereas IL-1 alpha and IL-6 had no effect, although all of these cytokines are inducible by LPS. LPS stimulation in the presence of cycloheximide decreased the LPS-mediated C3 mRNA induction by 60%. These data suggest that LPS effect on C3 regulation is mediated directly by LPS as well as by LPS-induced cytokines. Interestingly, C3 mRNA induced by Newcastle disease virus or inactivated Newcastle disease virus was inhibited by protein kinase inhibitors, H-7 and staurosporine, whereas these inhibitors had no effect on C3 induction mediated by LPS or cytokines, indicating the existence of different signal transduction pathways.
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PMID:Induction of C3 expression in astrocytes is regulated by cytokines and Newcastle disease virus. 153 Sep 57

Interleukin-8 (IL-8) is a neutrophil and lymphocyte chemoattractant and activator that may play an important role in mediating events at sites of inflammation. IL-8 is produced by many cell types in response to a variety of inducers, including interleukin-1 (IL-1). Studies were conducted to address the question of whether an inhibitor of IL-1 action, IL-1 receptor antagonist protein (IRAP), would suppress IL-8 production. Lipopolysaccharide (LPS)-stimulated human whole blood was used as an ex vivo model of local cytokine production. Preliminary time course studies showed that plasma IL-1 beta levels were fully induced by 6 hours (approximately 15 ng/ml) and persisted at this level over 24 hours. IL-8 production, in contrast, reached a plateau between 6 to 12 hours (5 ng/ml) and then increased rapidly to 17 ng/ml at 24 hours. Addition of IRAP was found to dose-dependently inhibit IL-8 expression at the levels of both protein and mRNA. A 50% reduction in IL-8 protein release occurred at an IRAP dose of 8 micrograms/ml (5 x 10(-7) mol/l) at 24 hours. A 2 hour delay in the addition of IRAP relative to LPS still permitted optimal reduction in IL-8 release, whereas delays of 4-8 hours reduced or eliminated the inhibitory effect. IRAP was found to have no effect on the LPS-stimulated production of IL-1 alpha or IL-1 beta. In addition, experiments performed with isolated peripheral blood cells demonstrated that, whereas monocytes were the major producers of IL-8, IRAP was equally effective in reducing IL-8 production in neutrophil and mononuclear cell suspensions. These studies further document the role of IL-1 in inducing the production of IL-8 and indicate that the ability of IRAP to suppress IL-8 expression may be an important mechanism of the anti-inflammatory properties of this molecule.
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PMID:Interleukin-1 receptor antagonist protein inhibits interleukin-8 expression in lipopolysaccharide-stimulated human whole blood. 153 50

IL-8, a cytokine known for its potent and specific neutrophil activation and chemoattractant properties, has been recently detected in the circulation during septic shock, endotoxemia, and after IL-1 alpha administration. Because of its observed in vitro actions, it has been hypothesized that IL-8 may contribute to the dynamics of circulating granulocytes and to the pathologic sequelae seen in sepsis. Here, human rIL-8 is administered to healthy nonhuman primates as a single i.v. injection or as a continuous 8-h i.v. infusion. We demonstrate that both methods of i.v. administration result in a rapid but transient, severe granulocytopenia, followed by a granulocytosis that persists as long as IL-8 levels are detectable in the circulation. There were no hemodynamic changes after IL-8 administration, and animals remained clinically stable during the 24-h observation period. No detectable circulating TNF-alpha, IL-1 beta, or IL-6 response was induced by either IL-8 administration regimen. Histopathologic examination revealed mild to moderate neutrophilic margination in lung, liver, and spleen, of greater severity in baboons receiving the 8-h infusion. There was no associated neutrophilic infiltration or tissue injury. Thus, IL-8 modulates circulating granulocyte dynamics and likely directs their actions, but when administered i.v. to healthy animals, either as a bolus dose or as a continuous infusion for up to 8 h, does not induce the hemodynamic and metabolic aberrations or the acute organ damage seen during sepsis.
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PMID:Effects of intravenous IL-8 administration in nonhuman primates. 154 15

TNF, IL-1, and IL-6 are integral components of the cytokine cascade released in the response to inflammatory stimuli such as LPS. IL-8 is produced both in response to LPS as well as TNF and IL-1. The early, local production of TNF and IL-1 may therefore contribute to the subsequent expression of IL-8. This hypothesis was tested using LPS-stimulated human whole blood as an ex vivo model of local cytokine production. The production of TNF, IL-1 alpha, IL-1 beta, IL-6, and IL-8 was found to be responsive to a wide range of LPS concentrations (0.1 ng/ml-10 micrograms/ml). These cytokines were first detected between 1 to 4 h post-LPS stimulation, and reached plateau levels after 6 to 12 h. IL-8, however, also displayed a secondary wave of production, with the levels again increasing between 12 to 24 h. The IL-8 present in the plasma after LPS stimulation was biologically active, as assessed by neutrophil chemotaxis. In further studies, addition of anti-TNF and anti-IL-1 neutralizing antibodies, alone and in combination, to LPS-stimulated blood resulted in nearly complete ablation of the secondary phase of IL-8 synthesis at both the levels of protein and mRNA, while leaving the first, LPS-mediated phase of IL-8 synthesis unaffected. This model of cytokine production in human whole blood may reflect the sequence of events in a localized environment of inflammation where both a primary stimulus and the induced early cytokine mediators may serve to elicit multiple, temporally distinct phases of IL-8 production.
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PMID:Biphasic production of IL-8 in lipopolysaccharide (LPS)-stimulated human whole blood. Separation of LPS- and cytokine-stimulated components using anti-tumor necrosis factor and anti-IL-1 antibodies. 154 21

The influence of cytokines on extracellular superoxide dismutase (EC-SOD) expression by human dermal fibroblasts was investigated. The expression was markedly stimulated by interferon-gamma (IFN-gamma), was varying between fibroblast lines stimulated or depressed by interleukin-1 alpha (IL-1 alpha), was intermediately depressed by tumor necrosis factor-alpha (TNF-alpha), and markedly depressed by transforming growth factor-beta (TGF-beta). TNF-alpha, however, enhanced the stimulation by a high dose of IFN-gamma, whereas TGF-beta markedly depressed the stimulations given by IFN-gamma and IL-1 alpha. The ratio between the maximal stimulation and depression observed was around 30-fold. The responses were generally slow and developed over periods of several days. There were no effects of IFN-alpha, IL-2, IL-3, IL-4, IL-6, IL-8, granulocyte-macrophage colony-stimulating factor, human growth hormone, Escherichia coli lipopolysaccharide, leukotriene B4, prostaglandin E2, formylmethionylleucylphenylalanine, platelet-activating factor, and indomethacin. The cytokines influencing the EC-SOD expression are also known to influence superoxide production by leukocytes and other cell types, and the EC-SOD response pattern is roughly compatible with the notion that its function is to protect cells against extracellular superoxide radicals. The results show that EC-SOD is a participant in the complex inflammatory response orchestrated by cytokines. The CuZn-SOD activity of the fibroblasts was not influenced by any of the cytokines, whereas the Mn-SOD activity was depressed by TGF-beta. TNF-alpha, IL-1 alpha, and IFN-gamma stimulated the Mn-SOD activity, as previously known, and these responses were reduced by TGF-beta. The different responses of the three SOD isoenzymes illustrate their different physiological roles.
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PMID:Regulation by cytokines of extracellular superoxide dismutase and other superoxide dismutase isoenzymes in fibroblasts. 155 78


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