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)

Interleukin-8 (IL-8), a chemotactic cytokine for T lymphocytes and neutrophils, is induced in several cell types by a variety of stimuli including the inflammatory cytokines IL-1 and tumor necrosis factor alpha TNF-alpha. Several cis elements, including a binding site for the inducible transcription factor NF-kappa B, have been identified in the regulatory region of the IL-8 gene. We have examined the ability of various NF-kappa B subunits to bind to, and activate transcription from, the IL-8 promoter. A nuclear complex was induced in phorbol myristate acetate-treated Jurkat T cells which bound specifically to the kappa B site of the IL-8 promoter and was inhibited by addition of purified I kappa B alpha to the reaction mixture. Only antibody to RelA (p65), but not to NFKB1 (p50), NFKB2 (p50B), c-Rel, or RelB was able to abolish binding, suggesting that RelA is a major component in these kappa B binding complexes. Gel mobility shift analysis with in vitro-translated and purified proteins indicated that whereas the kappa B element in the human immunodeficiency virus type 1 long terminal repeat bound to all members of the kappa B/Rel family examined, the IL-8 kappa B site bound only to RelA and to c-Rel and NFKB2 homodimers, but not to NFKB1 homodimers or heterodimers of NFKB1-RelA. Transient transfection analysis demonstrated a kappa B-dependent expression of the IL-8 promoter in a human fibrosarcoma cell line (8387) and in Jurkat T lymphocytes. Cotransfection with various NF-kappa B subunits indicated that RelA and c-Rel, but neither NFKB1 nor heterodimeric NFKB1-RelA, was able to activate transcription from the IL-8 promoter. Furthermore, cotransfection of NFKB1 and RelA, although able to support activation from the human immunodeficiency virus type 1 long terminal repeat, failed to activate expression from the IL-8 promoter. Antisense oligonucleotides to RelA, but not NFKB1, inhibited phorbol myristate acetate-induced IL-8 production in Jurkat T lymphocytes. These data demonstrate the differential ability of members of the kappa B/Rel family to bind to, and activate transcription from, the IL-8 promoter. Furthermore, while providing a novel example of a kappa B-regulated promoter in which the classical NF-kappa B complex is unable to activate transcription from the kappa B element, these data provide direct evidence for the role of RelA in regulation of IL-8 gene expression.
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PMID:NF-kappa B subunit-specific regulation of the interleukin-8 promoter. 841 15

Neutrophils are possibly involved in the pathogenesis of various lung diseases through the release of numerous mediators. In the present study, we studied the regulation of IL-8 gene induction and protein secretion in human blood neutrophils. Northern blot analysis revealed that LPS increased IL-8 mRNA levels in neutrophils, with a maximal fivefold increase by 2 h. IL-8 mRNa levels returned to baseline values within 12 h. In contrast, LPS-stimulated monocytes demonstrated a sustained increase of IL-8 mRNA levels for more than 24 h. TNF-alpha, IL-1 beta, and phorbol myristate acetate also increased IL-8 mRNA levels in neutrophils. Immunohistochemical analysis confirmed that IL-8 was localized within stimulated neutrophils. IL-8 secretion by neutrophils and monocytes was quantified using a specific ELISA for IL-8. Resting neutrophils secreted minimal IL-8 activity. However when cells were stimulated with LPS, TNF-alpha, or IL-1B, neutrophils secreted IL-8. IL-8 secretion was most marked during the first 2 h after stimulation and decreased thereafter. In contrast, monocytes maintained a high rate of IL-8 secretion over 12 h. Although a single monocyte secreted 70-fold more IL-8 than did a single neutrophil after 4 h of incubation, the high abundance of neutrophils in peripheral blood made the neutrophil-secreted IL-8 more significant. During the first 2 h, neutrophils secreted approximately 40% of the IL-8 released by monocytes in the same volume of blood. This ratio decreased to 9% after 12 h. Neutrophil-secreted IL-8 may play an autocrine or paracrine role during the initial stage of inflammation.
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PMID:Regulation of neutrophil interleukin 8 gene expression and protein secretion by LPS, TNF-alpha, and IL-1 beta. 843 97

Few known genes (IL-2, members of the IL-8 family, interferon-gamma) are induced in T cells only through the combined effect of phorbol myristic acetate (PMA) and a Ca(2+)-ionophore, and expression of only these genes can be fully suppressed by Cyclosporin A (CyA). We have identified a putative transcription factor, designated PILOT, with an identical dual signal requirement for expression. Induction of the PILOT gene is detectable in human T cells 20 min following activation in the presence of cycloheximide and is fully suppressed by CyA. The PILOT protein has a calculated M(r) of 42.6 kDa and contains three zinc fingers of the C2H2-type at the carboxyl-terminus which are highly homologous to the zinc finger regions of the transcription factors EGR1, EGR2, and pAT 133. In contrast to T cells, in fibroblasts PILOT gene expression requires only one signal (PMA) and is not affected by CyA. This observation directly demonstrates the existence of a Ca2+ signal-dependent regulatory element obligatory for expression of some genes in T cells but not in fibroblasts. This differential expression model will be valuable in the dissection of the dual signal pathway in T cells and the effects of CyA upon it.
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PMID:Expression of PILOT, a putative transcription factor, requires two signals and is cyclosporin A sensitive in T cells. 844 22

To evaluate the changes in cellular components and cytokine levels (tumor necrosis factor, interleukin-6 and IL-8) before and after intrapleural tetracycline (TC) injection, we evaluated 10 patients with malignant pleural effusion. Differential cell counts in the pleural fluid were obtained using cytocentrifuge preparations. Mononuclear cells from pleural fluid, collected before intrapleural injection of TC, on Day 4, and Days 10 to 14 after TC injection, were stimulated either with phytohemagglutinin (PHA) or PHA plus phorbol myristic acetate. The production of tumor necrosis factor (TNF) and IL-8 was measured. In addition, IL-6, IL-8, and TNF from serial collections of pleural fluid in these patients were measured by RIA or ELISA. The main inflammatory cells in pleural effusions before therapy were lymphocytes and mononuclear cells, but neutrophils predominated after TC injection. IL-6, IL-8, and TNF were markedly increased on Day 4 after TC intrapleural injection and then decreased to baseline levels on Day 14. The results suggest that TC intrapleural injection induces the release of cytokines (IL-6 and TNF), which are markers of an inflammatory response, and releases IL-8, which attracts neutrophils into the pleural space, which may be the mechanism of the sclerosing effect of TC.
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PMID:Changes in cell population and tumor necrosis factor, interleukin-6, and interleukin-8 in malignant pleural effusions after treatment with intrapleural tetracycline. 850 62

Since glucocorticoid effects on inflammatory processes may be mediated via modulation of cytokine release, different types of myelomonocytic cells were stimulated in vitro with lipopolysaccharide (50 ng/ml) or phorbol myristate acetate (25 ng/ml) plus the ionophore A23187, 2 x 10(-7) M, and release of interleukin (IL)-1 beta, IL-8 and tumor necrosis factor (TNF)-alpha was measured after 24 h by ELISA. Peripheral blood mononuclear cells from two allergic and two normal human donors released similarly large quantities of IL-8 and lower amounts of IL-1 beta and TNF-alpha. This also held for myelomonocytic cell lines, with THP-1 cells being most active, followed by U-937 and HL-60 cells. All potent glucocorticoids studied caused a dose-dependent inhibition of cytokine release from donor cells, being most marked for IL-1 beta and lowest for IL-8. Inhibition of cytokine release was also noted with U-937 cells, with clear differences in potency between the glucocorticoids, whereas release was enhanced in all experiments with THP-1 cells. These results were confirmed with Northern blot analysis. Modulating effects of glucocorticoids on cytokine release are thus complex, and are particularly dependent on the cell type studied.
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PMID:Glucocorticoid-induced modulation of cytokine secretion from normal and leukemic human myelomonocytic cells. 856 84

Gamma-interferon (IFN-gamma) is produced by T cells and plays an important role in immunological and inflammatory processes. To determine the effects of IFN-gamma on interleukin (IL)-6 and IL-8 secretion, normal human keratinocytes (NHKs), human squamous cell carcinoma cell line (HSC-1) cells, and human dermal fibroblasts (HDFs) were incubated with 100 U/ml of recombinant (r) IFN-gamma in the presence of various stimulants. HSC-1 cells and HDFs spontaneously secreted both IL-6 and IL-8 into the culture medium. NHKs secreted detectable levels of IL-8, but not of IL-6, and IL-8 secretion increased over 20 fold by stimulation with 10 nM of phorbol 12-myristate 13-acetate (PMA). rIFN-gamma inhibited IL-8 secretion in both HSC-1 cells and PMA-stimulated NHKs. On the other hand, it enhanced IL-1 alpha- and TNF alpha-induced IL-8 secretion in NHKs. In HDFs, rIFN-gamma inhibited IL-8 secretion, but enhanced secretion of IL-6, regardless of whether they were stimulated with IL-1 alpha or PMA. These results suggest that IFN-gamma has different regulatory effects on IL-6 and IL-8 secretion in NHKs and HDFs, depending on the stimulus.
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PMID:Regulatory effects of gamma-interferon on IL-6 and IL-8 secretion by cultured human keratinocytes and dermal fibroblasts. 864 94

Interleukin-8 (IL-8) is regarded as an important mediator of inflammation because of its potent and specific chemotactic activity on neutrophils. In the present investigation, human umbilical vein endothelial cells (HUVEC) stimulated with thrombin were found to produce IL-8, in a dose- and time-dependent manner. After stimulation with 10 U/ml thrombin for 24 hr, the level of IL-8 in the conditioned medium was 14 ng/ml, or enough to elicit PMN chemotaxis in vitro. Northern blot analysis revealed that thrombin as well as IL-1 beta elevates the level of IL-8 mRNA preceding the formation of IL-8 protein. A synthetic peptide SFLLRN [human thrombin receptor-activating peptide (TRAP)] was found to mimic the action of thrombin. Preincubation with anti-thrombin compounds such as hirudin and antithrombin-III-heparin almost completely suppressed the action of thrombin without affecting the actions of other stimuli including IL-1 beta, phorbol 12-myristate 13-acetate (PMA) and TRAP. Diisopropylfluorophosphate-treated thrombin did not stimulate IL-8 production. Calphostin-C, a protein kinase C (PKC) inhibitor, attenuated the production of IL-8 by thrombin, TRAP and PMA, but left the action of IL-1 beta unchanged. These results strongly suggest that catalytic activation of thrombin receptor by thrombin results in PKC-dependent IL-8 production accompanied by an increase in IL-8 mRNA level.
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PMID:Thrombin stimulates production of interleukin-8 in human umbilical vein endothelial cells. 870 54

Mast cells are well known effector cells not only in allergic but also in diverse acute and chronic inflammatory diseases. We have shown previously that these cells produce a broad spectrum of cytokines which might contribute to mast cell-dependent pathology. In the present study, we have investigated the influence of four potent glucocorticoids, methylprednisolone-aceponate, methylprednisolone-17-propionate, prednicarbate, and betametasone valerate (10(-5) M-10(-9) M), on the IL-1 beta, IL-3, IL-8, and tumor necrosis factor alpha secretion of the HMC-1 mast cell line as measured by ELISA. All four glucocorticoids caused a comparable dose- and time-dependent inhibition of cytokine release from HMC-1 cells stimulated for 24 h with phorbol 12-myristate 13-acetate 25 ng/ml and calcium ionophore 2 x 10(-7) M. These results shed further light on the mechanisms involved in antiinflammatory effects of glucocorticoids in allergic inflammation.
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PMID:Modulation of in vitro cytokine release from human leukemic mast cells (HMC-1) by glucocorticoids. 872 2

The way in which an antibiotic interacts with host defences could influence the clinical outcome of many infectious diseases. The impact of RO 23-9424, a novel dual-action and extended-spectrum antibiotic, was studied on several functions of human polymorphonuclear neutrophils (PMNs). A significant (P < 0.05) increase of the superoxide (O2-) released by phorbol-myristate acetate (PMA) -stimulated PMN (10-100 mg/L) can be observed in the RO 23-9424 pre-treated cells. RO 23-9424, particularly at low dosages, showed an interesting but not statistically significant effect on PMN phagocytosis. Higher dosages of RO 23-9424 (50-200 mg/L) and fleroxacin (20-200 mg/L) significantly reduced PMN chemotaxis. Cytokine production by human monocytes were also evaluated after incubation with the antibiotic (100-200 mg/L) in both basal conditions and in response to endotoxin (lipopolysaccharide, LPS). In the LPS-treated cells, RO 23-9424 (100 mg/L) significantly (P < 0.05) enhanced the tumour necrosis factor-alpha (TNF-alpha) levels, compared with LPS controls after 4 h of incubation. RO 23-9424 (200 mg/L) was able to reduce in a dose-dependent way LPS-induced interleukin-1 beta (IL-1 beta) after 4 and 24 h of incubation. Interleukin-8 (IL-8) release was not significantly changed by RO 23-9424. Cefotaxime (200 mg/L) significantly (P < 0.05) increased the basal levels of IL-1 beta and reduced basal IL-8 concentration after 24 h of incubation. The lower concentration of cefotaxime reduced the LPS-stimulated IL-8 levels. Fleroxacin (100 mg/L) enhanced basal levels of IL-8. The potentiated PMN phagocytosis, the significantly enhanced O2- release by PMA-stimulated PMN and the dimetric changes of TNF-alpha and IL-1 beta appeared peculiar for RO 23-9424 and may have useful therapeutical implications.
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PMID:Effect of RO 23-9424, cefotaxime and fleroxacin on functions of human polymorphonuclear cells and cytokine production by human monocytes. 896 Oct 49

The kinetics of IL-8, tumour necrosis factor-alpha (TNF-alpha) and IL-1 beta release by PMN adhered to fibronectin, laminin or plastic for 24 h in response to continuous stimulation with lipopolysaccharide (LPS; 50 ng/ml), N-formyl-Met-Leu-Phe (fMLP; 100 mM), or phorbol myristate acetate (PMA; 10 ng/ml), was investigated under altered oxygen tension conditions. Cell supernatants were sampled for cytokine content every 6 h and measured by ELISA. IL-8 was the most abundant cytokine, produced in a range of up to 5.4 ng/ml; TNF-alpha and IL-1 beta were produced in a range of up to 1 ng/ml. During normoxia, LPS was the most potent stimulus, inducing the release of each cytokine, while fMLP showed a less pronounced effect on IL-8 and IL-1 beta production and markedly inhibited TNF-alpha production. PMA markedly suppressed IL-8 and IL-1 beta release and failed to induce any release of TNF-alpha. Hypoxia had an overall inhibitory effect on cytokine release except for PMA-induced IL-1 beta release, and hypoxia/reoxygenation had a significant up-regulating effect except for a further inhibition of fMLP-induced release of TNF-alpha. Integrinmatrix protein ligation differentiated both spontaneous and externally induced cytokine release and its sensitivity to alteration in oxygen tension. Thus the process of PMN elaboration of inflammatory cytokines is controlled on multiple levels of signal transduction, differentiated by integrin-extracellular matrix interactions, and is sensitive to alterations in microenvironmental oxygen tension.
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PMID:Polymorphonuclear leucocyte (PMN)-derived inflammatory cytokines--regulation by oxygen tension and extracellular matrix. 897 28


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