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)

The liver participates in inflammation via the elaboration of acute phase proteins from hepatocytes in response to IL-1, TNF-alpha, and IL-6/INF-beta 2/hepatocyte-stimulating factor. In addition, some inflammatory states of the liver are characterized by leukocyte infiltrates. Here we demonstrate that human hepatocyte lines are capable of expressing mRNA and biologic activity for a neutrophil chemotactic factor (NCF)/IL-8 in response to the inflammatory mediators IL-1 alpha, IL-1 beta, and TNF. Two human hepatoma cell lines (SK-Hep and Hep-G2) displayed a time- and dose-dependent increase in steady state levels of NCF/IL-8 mRNA and secretion of chemotactic activity in response to TNF and IL-1. Neutralizing antibody to NCF/IL-8 inhibited hepatocyte-derived chemotactic activity by 88%. In contrast to IL-1 and TNF, hepatocytes did not respond to LPS or IL-6 within the time and dose parameters used above. Although the expression of NCF/IL-8 mRNA (1.8 kb) was first detectable between 1 and 2 h poststimulation, significant chemotactic bioactivity was not observed until about 4 h. Heat-inactivated (100 degrees C, 30 min) cytokine failed to induced NCF/IL-8 mRNA synthesis, and cotreatment of cells with cytokine and cycloheximide super-induced NCF/IL-8 mRNA while inhibiting production of bioactivity. Thus, NCF/IL-8 expression is a primary induction phenomenon. Our data demonstrate the stimulus specific induction of NCF/IL-8 in hepatocytes and suggest that cytokine cell-to-cell communication circuits may be important in neutrophil-mediated inflammatory processes in the liver.
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PMID:Cytokine-induced gene expression of a neutrophil chemotactic factor/IL-8 in human hepatocytes. 215 28

Human dermal fibroblasts in culture secrete three protein-like neutrophil chemotactic factors, when stimulated either with human rIL-1 alpha or IL-1 beta; not, however, after incubation with LPS. These three fibroblast-derived neutrophil-activating proteins (FINAP) could be purified by subsequently performed reversed phase and size exclusion HPLC. By high resolution SDS-PAGE, all the proteins were shown to migrate with an Mr of 6,700 (alpha-FINAP), 3,600 (beta-FINAP), and 5,300 (gamma-FINAP). All purified cytokine preparations were found to be chemotactic for human neutrophils. In addition, all FINAP induced release of lysosomal enzymes in neutrophils. Deactivation of chemotaxin-elicitable enzyme release showed cross-desensitization of all FINAP with NAP-1/IL-8. Western blot analysis of alpha-FINAP by using mAb against neutrophil-activating protein (NAP)-1/IL-8 reveals immunologic cross-reactivity with NAP-1/IL-8. By amino-terminal amino acid sequence analysis alpha-FINAP could be identified as the 77-residue extended form of NAP-1/IL-8 containing the 79-residue form as a minor contaminant. Whereas beta-FINAP has been found to be a truncation product of alpha-FINAP, gamma-FINAP shows identity with authentic melanoma growth stimulatory activity with respect to retention time upon reversed phase HPLC, high resolution SDS-PAGE, and biologic properties, as well as amino-terminal amino acid sequence. These data show that human dermal fibroblasts may actively participate in inflammatory reactions by secretion of proinflammatory cytokines.
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PMID:IL-1 alpha or tumor necrosis factor-alpha stimulate release of three NAP-1/IL-8-related neutrophil chemotactic proteins in human dermal fibroblasts. 217 8

Leucocytes and vascular cells interact closely in inflammation and immunity and cytokines are important mediators of this interaction. The present study was designed to define the capacity of human endothelial cells (HEC) to produce a monocyte-derived neutrophil chemotactic factor (provisionally termed IL-8). IL-8 is a polypeptide chemotactic for neutrophils originally identified in the culture supernatant of lipopolysaccharide (LPS)-stimulated monocytes. IL-1 induced high levels of production of neutrophil chemotactic activity in culture supernatants of HEC. Optimal stimulation of activity was observed when HEC were cultured with 10-100 ng/ml IL-1 beta for 16 hr. Anti-IL-8 antibody blocked the chemotactic activity for neutrophils of IL-1-activated HEC supernatants. IL-1-treated HEC expressed high levels of IL-8 mRNA transcripts, as assessed by Northern blot analysis. Tumour necrosis factor (TNF) and LPS, unlike the inflammatory monokine IL-6, also induced IL-8 expression. Nuclear run-off experiments revealed that IL-1 activated transcription of the IL-8 gene. The production of IL-8 may represent a mechanism whereby endothelial cells, exposed to inflammatory signals, participate in the regulation of neutrophil extravasation.
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PMID:IL-1 transcriptionally activates the neutrophil chemotactic factor/IL-8 gene in endothelial cells. 218 85

Interleukins (IL) are a heterogeneous class of cytokines involved in activation of T lymphocytes (IL-1, 2, 4, 6 and 7), B lymphocytes (IL-1, 2, 4, 5, 6 and 7), and macrophages (IL-1 and 4), and hematopoiesis (IL-1, 2, 3, 4, 5, 6 and 7), acting either by themselves, or as co-stimulator factors. Interleukin-1 (IL-1 alpha and IL-1 beta) is induced by different signals including microbial products; it mediates various events occurring during inflammation (e.g. fever, osteolysis, leucopenia, hypotension, hyperalgia, etc...). Such mechanisms are often the consequences of the induction by IL-1 of lipid mediators (e.g. prostaglandins, platelet activating factor, etc). IL-1 often acts synergistically with Tumor Necrosis Factor during the pro-inflammatory process. IL-1 as well as microbial products induces the production of interleukin-6 and interleukin-8. IL-6 also plays a role in inflammation, mainly as an inducer of acute phase proteins synthesis by hepatocytes. IL-8 has chemotactic and activating properties for neutrophils.
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PMID:[Interleukins and inflammation]. 230 78

Adherence of monocytes to endothelial cells or extracellular matrices is likely to play a critical role in triggering monocyte activation in extravascular sites of infection, chronic inflammatory disorders, tissue damage and neoplastic growth. We have constructed a cDNA library from monocytes adhered for 30 min on plastic and have screened it by differential hybridization for mRNA rapidly induced by adherence. Two of the cDNA isolated have been identified as IL-1 beta and superoxide dismutase. Sequence data from three other adherence specific clones demonstrates the presence of ATTTA mRNA instability sequences in their 3' untranslated regions signifying inflammation-associated genes. The deduced amino acid sequences indicate the presence of open reading frames with sequence homologies to a family of host defense cytokines, one of them being identified as IL-8. Of the 14 clones initially identified, 4 have been analyzed for induction of mRNA expression. Although 3 of the 4 clones were equally induced by PMA and LPS under nonadherent conditions, all 4 cDNA showed distinct patterns of induction with adherence to extracellular matrix components or endothelial cells. The deduced amino acid sequence homologies indicate that we have isolated cDNA that code for three unique gene products. These cDNA belong to a gene family of early host defense cytokines involved in inflammation and cell growth, but which are differentially regulated by adherence to different surfaces.
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PMID:Monocyte adherence results in selective induction of novel genes sharing homology with mediators of inflammation and tissue repair. 234 26

The influence of human monocyte-derived chemotactic peptide (GCP/IL-8) on degranulation of neutrophils was investigated in relation to that of other monokines. GCP/IL-8 promoted a dose-dependent release of lactoferrin from specific granules but had no effect on enzyme release from primary granules. From the other monokines that were tested, tumour necrosis factor alpha (TNF alpha) also induced degranulation, while IL-1 beta and IL-6 scored negatively. TNF alpha-induced lactoferrin release was enhanced by cytochalasin B pretreatment of the granulocytes, while GCP/IL-8-promoted degranulation was not. In contrast to GCP, TNF alpha also caused the release of LDH, suggesting a non-specific cell destruction. These observations further support the view that, unlike the other monokines, GCP/IL-8 is a true and specific granulocyte activator.
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PMID:Human granulocyte chemotactic peptide (IL-8) as a specific neutrophil degranulator: comparison with other monokines. 267 Jul 52

The role of calcium in interleukin- (IL) 8-, IL-1 alpha- and IL-1 beta-induced lymphocyte migration has been investigated by using the calcium channel antagonists, verapamil, nifedipine, diltiazem (IL-8) and the optical isomers of the dihydropyridine analogue SDZ 202-791 (IL-8, IL-1 alpha and IL-1 beta). Potent inhibition of IL-8-induced migration was observed in response to nifedipine (IC50 = 10 nM), verapamil (IC50 = 60 nM) and diltiazem (IC50 = 10 nM). The (+)-isomer of SDZ 202-791 was without effect on any of the agonists tested, however, the (-)-isomer induced dose-related inhibition of stimulated migration, IC50 values being 0.1 nM, 10 pM and 1.0 nM, for IL-8-, IL-1 alpha- and IL-1 beta-induced migration, respectively. Reversal of the inhibitory effects of the (-)-isomer was obtained in the presence of increasing concentrations of (+)-isomer. The induction of lymphocyte migration by IL-8, IL-1 alpha and IL-1 beta therefore appears to be a process dependent on calcium channel activation.
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PMID:Potent and specific inhibition of IL-8-, IL-1 alpha- and IL-1 beta-induced in vitro human lymphocyte migration by calcium channel antagonists. 268 46

A factor able to induce an early local inflammation in rabbit skin was detected in the supernatant of mitogen-stimulated human blood leukocytes. The factor was different from IL-1 which, although present in the supernatants, was chemically separable from the factor and induced a late rather than an early skin response. Other biological effects of the principal factor were its in vitro chemotactic effects on granulocytes and its ability to induce rapid granulocytosis upon intravenous injection in rabbits. When tested under the same conditions, IL-1 beta did not act chemotactically and induced granulocytosis at a later time. The factor was purified to homogeneity and identified by electrophoretic mobility as a protein of Mr 6,500. Amino acid sequence analysis revealed the presence of an uncontaminated NH2-terminal sequence identical to a segment of the sequence previously predicted from the cDNA clone (3-10C) copied from an mRNA isolated from human leukocytes and coding for a protein of unknown function. The NH2-terminal sequence of the factor also showed extensive homology to that of the platelet factors beta-thromboglobulin (beta TG) and platelet factor 4 (PF-4). Studies done to identify the cell source of the factor revealed that it was produced by adherent mononuclear cells but not by platelets, while the opposite was true for beta TG.
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PMID:A novel, NH2-terminal sequence-characterized human monokine possessing neutrophil chemotactic, skin-reactive, and granulocytosis-promoting activity. 325 25

We used a whole-gut perfusion technique to study subclinical gut inflammation in children with cystic fibrosis (18 elective tests, three lavages to treat distal intestinal obstruction syndrome); and in 12 control children with constipation or pre-colonoscopy. We assayed for haemoglobin, IgG, albumin, alpha-1-antitrypsin, granulocyte elastase, interleukin-1 beta (IL-1 beta) and IL-8 concentrations in whole-gut lavage fluid. Results for two children with distal intestinal obstruction syndrome, the only children in the series taking Nutrizym 22, were strikingly abnormal. This new test has revealed subclinical gut mucosal inflammation in a minority of CF children, for which distal intestinal obstruction syndrome, Nutrizym 22 treatment, or both, may be risk factors.
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PMID:Gut inflammation in children with cystic fibrosis on high-dose enzyme supplements. 856 82

Previous findings provided evidence that bacterial lipopolysaccharide (LPS)-activated human monocytes are able to upregulate autologous polymorphonuclear (PMN) phagocytic ability via cell-to-cell contact mechanisms mediated by membrane (m)-associated cytokines (CKs), such as tumour necrosis factor (TNF)-alpha, interleukin (IL)-1 alpha, IL-1 beta, IL-6 and IL-8. Consequently, the role of the lymphocyte function-associated antigen (LFA)-1 molecule on the monocyte (Mo)-PMN interplay was evaluated. In the first step, lipid A (LA)-stimulated Mo were pretreated with anti-recombinant human (Rhu) LFA-1 alpha monoclonal antibody (MoAb), and the enhanced phagocytic activity of PMN was abrogated. Pretreatment of unstimulated Mo with the same MoAb led to a reduction of PMN phagocytosis. In the second step, the role of m-LFA-1 on PMN was investigated with regard to Mo modulation. Anti-Rhu LFA-1 alpha MoAb was supplemented to LA-activated and unstimulated PMN, respectively, before coculturing with autologous LA-activated Mo. The addition of anti-Rhu LFA-1 alpha MoAb gave rise to a significant decrease in PMN phagocytosis regardless of PMN activation. These data suggest that, besides m-CKs, LFA-1 present on Mo and PMN might be involved in the mutual interplay between PMN and Mo.
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PMID:Role of lymphocyte function-associated antigen-1 on the interplay between lipid A-activated monocytes and polymorphonuclear cells. 747 67


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