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)

Leukocyte recruitment is critical in the inflammation seen in rheumatoid arthritis (RA). To determine whether the chemokine growth-related gene product alpha (gro alpha) plays a role in this process, we examined synovial tissue (ST), synovial fluid (SF), and plasma samples from 102 patients with arthritis. RA SF contained more antigenic gro alpha (mean 5.3 +/- 1.9 ng/ml) than did SFs from either osteoarthritis (OA) or other forms of arthritis (mean 0.1 ng/ml) (p < 0.05). RA plasma contained more gro alpha (mean 4.3 +/- 1.8 ng/ml) than normal plasma (mean 0.1 ng/ml) (p < 0.05). RA ST fibroblasts (1.2 x 10(5)/cells/mI RPMI 1640/24 h) produced antigenic gro alpha (mean 0.2 +/- 0.1 ng/ml), and this production was increased significantly upon incubation with TNF-alpha (mean 1.3 +/- 0.3 ng/ml) or IL-1 beta (mean 2.3 +/- 0.6 ng/ml) (p < 0.05). Cells from RA SF also produced gro alpha: neutrophils (PMNs) (10(7) cells/mI/24 h) produced 3.7 +/- 0.7 ng/ml. RA SF mononuclear cells produced gro alpha, particularly upon incubation with LPS or PHA. Immunoreactive ST gro alpha was found in greater numbers of RA compared with either OA or normal lining cells, as well as in RA compared with OA subsynovial macrophages (p < 0.05). IL-8 accounted for a mean of 36% of the RA SF chemotactic activity for PMNs, while epithelial neutrophil-activating peptide-78 accounted for 34%, and gro alpha for 28%, of this activity. Combined neutralization of all three chemokines in RA SFs resulted in a mean decrease of 50% of the chemotactic activity for PMNs present in the RA SFs. These results indicate that gro alpha plays an important role in the ingress of PMNs into the RA joint.
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PMID:Growth-related gene product alpha. A chemotactic cytokine for neutrophils in rheumatoid arthritis. 756 Oct 66

Concentrations of MCP-1 and NAP-1 in culture fluids of human leukocytes were measured by sandwich ELISA. PPD caused PBMC's from tuberculin-sensitive subjects to secrete MCP-1 and NAP-1. PPD did not stimulate secretion by cells from a tuberculin-negative subject. Since the amounts secreted were more than could be produced by the few PPD-sensitized lymphocytes in the culture, we postulate that other cells were stimulated to secrete these chemoattractants. This study evaluated secretory capacity of one of the cell types in the PBMC culture. Unstimulated monocytes did not secrete MCP-1 or NAP-1. In order of increasing effect, IL-2 + IFN gamma, IL-1 alpha, and LPS caused monocyte secretion of MCP-1. The rank order for NAP-1 secretion was the same. TNF alpha did not cause secretion of MCP-1, but caused about the same amount of NAP-1 secretion as IL-2 + IFN gamma. Composition of the culture medium was especially critical for LPS-induced secretion of MCP-1, which was greatly enhanced by FCS and by Iscove's DMEM compared to RPMI 1640. IL-4 inhibited LPS-induced secretion of both MCP-1 and NAP-1. Secretory patterns were also a function of mononuclear phagocyte phenotype. LPS-induced secretion of MCP-1 was much greater for monocytes cultured several days in CSF-1 than for freshly isolated monocytes. LPS stimulation of bronchoalveolar macrophages caused NAP-1 secretion, but no secretion of MCP-1 above a relatively low baseline level.
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PMID:Secretion of monocyte chemoattractant protein-1 (MCP-1) by human mononuclear phagocytes. 794 99

Interleukin-8 (IL-8) is a potent chemotactic protein for polymorphonuclear leukocytes (PMN). Here we examine whether PMN synthesize and release IL-8 in response to stimulation by leukotriene B4 (LTB4). PMN isolated from normal heparinized peripheral human blood were incubated in RPMI culture medium at 37 degrees C in 5% CO2, with and without LTB4. The culture supernatants were tested for IL-8 bioactivity through chemotactic activity measurements with and without neutralizing anti-IL-8 serum. Immunoreactive IL-8 was quantified by ELISA, and de novo IL-8 synthesis was evaluated by metabolic labeling with [35S]cysteine followed by immunoprecipitation. LTB4 stimulated PMN to produce IL-8 in a dose- and time-dependent manner. The IL-8 concentrations reached maximal levels after 16 h of incubation with LTB4. Significant increases in IL-8 production occurred with LTB4 doses of 10 to 1,000 nM/ml. Immunoprecipitation of labeled IL-8 documented new synthesis of IL-8 by LTB4-treated PMN. Northern blot analysis of total RNA from PMN using a 30 mer oligonucleotide for IL-8 demonstrated increased mRNA expression in LTB4-stimulated PMN compared with untreated PMN. These data show that peripheral blood PMN can be stimulated by LTB4 to synthesize and secrete biologically active IL-8. PMN and other cells capable of producing LTB4 may induce IL-8 protein production by inflammatory PMN and thereby amplify or perpetuate the acute inflammatory response by recruiting additional PMN into an inflammatory site.
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PMID:Leukotriene B4 stimulates human polymorphonuclear leukocytes to synthesize and release interleukin-8 in vitro. 800 41

Interleukin-8 (IL-8) is a potent chemotactic factor for polymorphonuclear leukocytes (PMN). Here we examine whether PMN synthesize and release IL-8 in response to stimulation by selected inflammatory cytokines. PMN isolated from normal heparinized peripheral human blood were incubated in RPMI culture medium at 37 degrees C in 5% CO2, with and without granulocyte/macrophage colony-stimulating factor (GM-CSF). The culture supernatants were tested for chemotactic activity using a modified Boyden chamber. Immunoreactive IL-8 protein was measured by ELISA with a monoclonal antibody specific for IL-8. GM-CSF (0.01 to 50 ng/ml) stimulated PMN to produce chemotactic activity in a dose- and time-dependent manner. The amount of chemotactic activity reached maximal levels after 3 h of incubation with GM-CSF. Treatment of culture media supernatants with rabbit antiserum against IL-8 blocked the GM-CSF-induced chemotactic activity. IL-8 protein concentrations detected by ELISA closely paralleled the chemotactic bioactivity in both the dose-response and kinetic studies. Northern blot analysis of total RNA from PMN using a 30 mer oligonucleotide complementary to mRNA for IL-8 yielded a single 1.6-kb band. Its intensity increased 4-fold 2 h after treatment of PMN with GM-CSF. These data suggest that peripheral blood PMN can be stimulated by GM-CSF to synthesize and secrete bioactive IL-8. Since both IL-8 and GM-CSF accumulate in sites of acute inflammation, PMN may induce IL-8 gene expression in response to GM-CSF and thereby amplify the acute inflammatory response by recruiting additional PMN into inflammatory sites.
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PMID:Granulocyte/macrophage colony-stimulating factor stimulates human polymorphonuclear leukocytes to produce interleukin-8 in vitro. 841 54

It has been hypothesized that the development of cancer might partially result from a diminution of immunocompetence. Using ex vivo cytokine production by whole blood (WB) cells after polyclonal activation, we compared cytokine production levels of cancer patients to those of healthy controls. Seventeen patients without any prior treatment and attending the hospital for oncological surgery (for cancers of several origins) were enrolled in the study. WB was collected in heparinized tubes, diluted 1/10 in RPMI 1640 and incubated for 2, 4, 24, 48, and 72 h at 37 degrees C in the presence of 5 micrograms/ml PHA and 25 micrograms/ml LPS. Cytokine levels in the supernatant were measured by specific immunoassay kits. IL-10 levels after 24 h of culture, IFN-gamma and GM-CSF levels after 24 and 72 h of culture, and LIF levels after 72 h of culture were significantly lower in cancer patients than in healthy controls. No significant difference was observed for IL-1 beta, IL-2, IL-4, IL-8, and TNF-alpha production at any culture time. Our results suggest that the putative immunosuppression of cancer patients might be reflected by their reduced production of immunostimulated cytokines.
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PMID:Ex vivo cytokine production by whole blood cells from cancer patients. 876 14

/We have studied the effect of interferon alpha (IFN-alpha) on MHC class II expression by human buccal epithelial cells (BEC), and mRNA expression by BEC and mucosal-associated mononuclear cells (MAMC). In 6 experiments, freshly collected BEC were suspended at a concentration of 1.0 x 10(5)/ml in RPMI 1640 and incubated in the presence of 0-10,000 IU/ml of human lymphoblastoid IFN-alpha (HuIFN-alpha). Zero and six hour samples were analyzed by single color flow cytometry using FITC-labeled murine IgG1 monoclonal antibody to HLA-DR. Preparations were also analyzed for expression of cytokine transcripts (IL-2, IL-4, IL-5, IL-6, IL-8, IFN-gamma, GM-CSF) by reverse transcriptase polymerase chain reaction (RT-PCR). Increasing concentrations of IFN-alpha resulted in proportionate increases in the percentage of HLA-DR + BEC (r = 0.7897, p = 0.0627) and in the percentage of HLA-DR+ staining at higher intensities (10(1) to 10(2) log fluorescence intensity) (LFI) (r = 0.4010, p = 0.0424). The percentage of HLA-DR + BEC rose from a mean of 1.5% with no IFN-alpha to 7% with 10,000 IU/ml IFN-alpha (p < 0.05). The percentage of HLA-DR + BEC staining at 10(1) to 10(2) LFI rose from a mean of 8.3% with no added IFN-alpha to 19.2% with 10,000 IU/ml IFN-alpha (p < 0.05). Unstimulated BEC constitutively expressed IL-8 and GM-CSF. IFN-alpha stimulated preparations also expressed IFN-gamma, possibly due to the presence of MAMC, which comprised 2-9% of the total cell population. These data indicated that HuIFN-alpha upregulates MHC class II expression by human BEC, possibly by enhancing IFN-gamma production by MAMC present in the culture preparations.
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PMID:Effect of interferon alpha on HLA-DR expression by human buccal epithelial cells. 891 10

Chemokines play a very important role in inflammation and belong to the family of proinflammatory cytokines. They preferentially act on neutrophiles and have no activity on monocytes and eosinophiles. IL-8 is a member of C-X-C chemokines. The IL-8 level is about 150-times higher in the psoriasis affected skin. It suggests that IL-8 may play an important role in the pathogenesis of psoriasis. The precise mechanism of cyclosporine (CsA) and retinoic acid (RA) effects are not known. The aim of the experiment was to find out CsA effect and RA effect on production of IL-8 by THP-1 cell line. THP-1 cell line was cultivated in completed RPMI-1640 medium and stimulated with LPS. The level of IL-8 was evaluated by human ELISA kits. Student's test was used for statistical analysis. It was found out that CsA inhibits IL-8 production by stimulated THP-1 monocyte cell line in dose dependence course. RA promotes IL-8 production by stimulated THP-1 monocyte cell line in dose dependence course. Preincubation experiments with CsA and RA confirmed the previously found effects of these drugs. CsA did not demonstrate cytotoxic effect on THP-1 cell line. (Fig. 7, Tab. 6, Ref. 17.)
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PMID:[Production of IL-8 by the THP-1 monocyte cell line is regulated differently by cyclosporin and retinoic acid]. 958 80

Anticoagulants can influence production of cytokines in whole blood, but the effects vary depending on the type of anticoagulant and the immunological stimulus. We examined this further by anticoagulating normal blood with either unfractionated (UF) heparin or low molecular weight heparin (Fragmin) and stimulating each sample with lipopolysaccharide, zymosan A, phytohemagglutinin, immune complexes, H2O2, or RPMI. After incubating 24 h, the combination of lipopolysaccharide and Fragmin induced significantly greater concentrations of interleukin 1 (IL)-1beta (25+/-10 ng/mL; x +/- standard error), IL-8 (21+/-6), and tumor necrosis factor (TNF)alpha (.48+/-.24) compared with heparinized blood (p < .05). The combination of Fragmin and zymosan also induced significantly greater concentrations of IL-1beta (97+/-24) and TNFalpha (2.9+/-.8), but not IL-8 (2.0+/-15). Average levels of proinflammatory cytokines (IL-1beta, IL-6, IL-8, and TNFalpha) were greater with Fragmin anticoagulation for 36 of 40 comparisons, and patterns were similar for 6 h and 24 h incubations. Statistical difference was established in 33% of these comparisons. A composite score of proinflammatory cytokines for Fragmin-anticoagulated blood was significantly greater than expected for UF heparinized blood (p < .0001) after 24 h. Expression of one anti-inflammatory cytokine (IL-10) was only slightly elevated for Fragmin anticoagulation. Proinflammatory cytokines are produced in greater quantities with Fragmin anticoagulation, which may be a disadvantage for ischemic conditions (e.g., cardiac surgery) but advantageous for long-term treatment of thrombosis.
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PMID:Low molecular weight heparin is associated with greater cytokine production in a stimulated whole blood model. 974 47

Cytokine networks are important in regulating the traffic of inflammatory cells in the airways. Interleukin-8 (IL-8) released by human bronchial epithelial cells (HBECs) is thought to be of particular importance in attracting neutrophils and monocytes to sites of inflammation. Increased release of IL-8 by HBECs in response to Th-1 cytokines such as TNF alpha and IL-1 beta may be an important pathophysiologic pathway. The present study was designed to explore the role of the Th2 cytokine IL-4 and the functionally related interleukins IL-10, and IL-13 on the regulation of IL-8 release by HBECs. HBECs (passage 4-6) were cultured in LHC9/RPMI and when confluent cells were stimulated in unsupplemented medium LHCD/RPMI by IL-4, IL-10, and IL-13 at 10 ng/ml concentration for all cytokines. TNF alpha stimulation was used as a positive control. After 24 hours supernatants were collected and tested for IL-8 by a sandwich ELISA. Unstimulated HBECs spontaneously released limited amounts of IL-8 (11 +/-1 pM) and significantly increased cytokine production in response to IL-4 (42 +/- 1 pM), IL-13 (30 +/- 1 pM) and TNF (128 +/- 11 pM). Stimulation with IL-10 (11 +/- pM) did not change basal production of IL-8. When HBECs were co-stimulated with IL-4 plus TNF, the production of IL-8 was further increased (204 +/- 5 pM). In contrast, IL-10 attenuated the effect of TNF during co-stimulation (82 +/- 5 pM). IL-13 did not affect the release of IL-8 induced by TNF (111 +/- 9 pM). Northern blot analysis of IL-8 mRNA levels showed the highest induction of IL-8 mRNA in HBECs co-stimulated with TNF and IL-4. We conclude from our study that IL-4 directly induces IL-8 release from HBECs and amplifies the release of IL-8 in response to TNF alpha. IL-13 is less active and IL-10 has an inhibitory effect. Airway epithelial cells are able to interact, therefore, with products of both Th1 and Th2 cells with respect to modulating release of IL-8.
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PMID:IL-4 and IL-13 stimulate human bronchial epithelial cells to release IL-8. 1056 68

Packed red blood cell (PRBC) transfusion has been invoked previously with immunosuppression and increased infections, but it has now been demonstrated that stored PRBCs (>14 days) can prime PMNs and provoke multiple organ failure. Recently, the role of PMNs in the genesis of MOF has been extended to their release of inflammatory cytokines, notably IL-1, IL-8, TNFalpha, and secretory phospholipase A2 (sPLA2). We hypothesize that stored PRBCs can act as a second event via stimulating the release of inflammatory cytokines from PMNs. Isolated human PMNs were incubated for 24 h in RPMI with either 20% fresh plasma or plasma from 42 day old PRBC (day of outdate) and release of IL-8, IL-1beta, TNFalpha, and sPLA2 were measured. Plasma from stored PRBCs contained small amounts of IL-8, sPLA2, and TNFalpha (102.1 +/-5.6 pg/ml, 87.6+/-6.0 pg/ml and 9.7+/-.7 pg/ml). Levels of IL-1beta were below detection (<1 pg/ml). Day 42 PRBC plasma stimulated significant PMN release of both IL-8 and sPLA2 as compared to both control and day 0 plasma (*P < .05), but PRBC plasma did not stimulate PMN release of either IL-1beta or TNFalpha. Transfused blood is emerging as an inflammatory agent that is capable of producing PMN priming. In this study we have demonstrated that PRBC plasma selectively activates PMNs to release both IL-8 and sPLA2. Thus, transfusion of PRBCs may represent a preventable inflammatory insult via modification of both blood banking and transfusion practices.
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PMID:Stored red blood cells selectively activate human neutrophils to release IL-8 and secretory PLA2. 1063 66


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