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)

In response to exogenous stimuli such as phorbol-12-myristate 13-acetate, ultraviolet B radiation, and lipopolysaccharide, human keratinocytes produce soluble mediators that are important in primary contact irritancy including cytokines that are associated with proinflammatory properties (interleukin-1 alpha [IL-1 alpha], tumor necrosis factor alpha), chemotaxis (IL-8), and growth activation (granulocyte/macrophage colony stimulating factor, IL-6, transforming growth factor alpha). We examined qualitative and quantitative changes in selected intracellular and secreted cytokines in human keratinocyte cultures in response to non-sensitizing contact irritants (croton oil, sodium lauryl sulfate, methyl salicylate, ethyl phenylpropiolate), sensitizing irritants (oxazolone, dinitrofluorobenzene), and ulcerative agents (phenol, benzalkonium chloride, chromium trioxide). The chemicals were also applied to mouse skin to assess whether the chemical-specific pattern of inflammation correlated with the in vitro production of keratinocyte-derived cytokines. Although all agents elicited neutrophils to the site of chemical application, time dependent and chemical-specific patterns of inflammation could be detected. Sodium lauryl sulfate, phenol, and croton oil induced increases in IL-8 production at non-cytotoxic concentrations in semi-confluent human keratinocyte cultures. Phenol and croton oil stimulated tumor necrosis factor alpha production, whereas croton oil was the only agent found to induce granulocyte/macrophage colony-stimulating factor production. Croton oil, phenol, benzalkonium chloride, and dinitrofluorobenzene induced the intracellular production of IL-1 alpha without a concomitant release into the medium. The release of cytokines occurred in parallel with a relative increase in cytokine-specific mRNA transcripts. Studies using neutralizing antibodies to tumor necrosis factor alpha and IL-1 alpha demonstrated that IL-8 induction by croton oil and phenol occurred directly rather than through autocrine circuits. These data suggest that a given pattern of cytokine production is chemical-specific and may predict the contribution of keratinocytes to skin inflammation.
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PMID:Cytokine induction in human epidermal keratinocytes exposed to contact irritants and its relation to chemical-induced inflammation in mouse skin. 800 54

The interaction of interleukin 8 (IL-8) with heparin was studied by using synthetic IL-8 analogs with C- and N-terminal truncations. Elimination of the N-terminal region preceding the first cysteine, which constitutes the IL-8 receptor binding site, did not affect the affinity to heparin-Sepharose. Affinity, however, decreased with progressive truncation at the C terminus, and no binding was observed when the C-terminal alpha-helix was eliminated. The effect of heparin and other glycosaminoglycans on IL-8 activity was also tested. When IL-8 was applied together with heparan sulfate, neutrophil chemotaxis in vitro was enhanced up to 4-fold, and the stimulus-dependent increase in cytosolic free Ca2+ increased markedly in both rate and peak value. Heparin had a similar effect on the Ca2+ response but did not enhance chemotaxis. The glycosaminoglycans by themselves did not elicit neutrophil responses. Their enhancing effect was restricted to stimulation with IL-8 and was not observed when the unrelated chemoattractant fMet-Ile-Phe-Leu was used as the stimulus. Elastase released from stimulated neutrophils was inhibited by heparin, heparan sulfate, and, to a lesser extent, chondroitin sulfate B, confirming previous observations. Taken together, these results suggest that heparan sulfate, which is present on the endothelial cell surface and in the basement membrane, may have a dual function in diapedesis, promotion of IL-8-dependent transmigration of neutrophils, and protection of the tissue microenvironment from damage by lytic enzymes released from the migrating cells.
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PMID:Binding to heparan sulfate or heparin enhances neutrophil responses to interleukin 8. 834 30

Dendritic epidermal T cells (DETCs) are Thy-1+, CD45+, CD3+, CD4-, CD8-, and T-cell receptor-V gamma 3/V delta 1+ leukocytes that reside normally in adult mouse skin. We have demonstrated previously that keratinocytes serve as adhesion substrates for DETCs, and that interleukin 7 (IL-7), which is produced by keratinocytes, serves as a growth factor for DETCs. The present study was conducted to address the mechanisms by which DETCs migrate into the epidermis, reasoning that keratinocytes may also be a source of chemotactic activity. Short-term DETC lines were 35S-labeled and tested for migration toward Pam 212 keratinocyte culture supernatants using a modified Boyden chamber method; cell movement from upper chambers toward test samples in lower chambers was traced by counting radioactivity. DETC displayed rapid (within 60 min) and marked (> 50%) migration toward keratinocyte supernatants. The majority of cells that had migrated into keratinocyte supernatants expressed the V gamma 3 T-cell receptor, thus verifying that the migrating cells were DETCs. Addition of keratinocyte supernatants to the upper chambers completely blocked migration, suggesting its chemotactic nature. By contrast, no DETC migration was observed toward 3T3 fibroblast supernatants. Chemotactic activities were 1) produced by Pam 212 cells even in the absence of serum; 2) greater than 12 kD in size; 3) heat and pH labile; 4) trypsin sensitive; and 5) precipitated by 60-100% ammonium sulfate. Several cytokines (e.g., IL-1 alpha and IL-8) failed to mediate DETC migration when added to the lower chambers. Likewise, the same cytokines, when added to the upper chambers, failed to inhibit DETC migration toward Pam 212 supernatants. These results support our hypothesis that keratinocytes facilitate the residence of DETC in epidermis by secreting unique chemotactic factors, by providing adhesion substrates, and by elaborating specific growth factors.
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PMID:Mouse dendritic epidermal T cells exhibit chemotactic migration toward PAM 212 keratinocyte culture supernatants. 839 9

To clarify the mechanism of action of immunoglobulin (IgG) in intravenous immunoglobulin therapy for ulcerative colitis (UC) patients, we studied the effect of IgG on the dynamics of immunocompetent cells in the colonic mucosa of experimental colitis induced by dextran sulfate sodium (DSS) in rats. The administration of the same species' IgG suppressed the mucosal infiltration of immunocompetent cells (activated T cells, macrophages and neutrophils), although the different species' IgG didn't. We have already shown that the same species' IgG, suppressed the production of inflammatory cytokines (TNF alpha, IL-1 alpha and IL-8) in the colonic mucosa of experimental colitis induced by DSS. In the present report, we demonstrated the different species' IgG, as well as same species' IgG, suppressed the production of inflammatory cytokines (TNF alpha and IL-1 alpha) from lamina propria mononuclear cells of rat large intestine in vitro. Therefore, it was considered that the suppression of cytokine production was a consequence of the decreased immunocompetent cells in colitis mucosa. Furthermore, we demonstrated that the DSS-treated antigen presenting cells (APCs) activated antigen-specific T cells as a possible mechanism underlying the colitis induced by DSS and the same species' IgG inhibited this activation of T cells.
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PMID:[Immunological effect of immunoglobulin on experimental colitis induced by dextran sulfate]. 855 75

The A549 cell line was used to model in vitro the interaction of alveolar epithelium with environmental particulates. Confocal and electron microscopy demonstrated A549 binding and internalization of titanium dioxide (TiO2), iron oxide (Fe2O3), concentrated ambient air particulates (CAPs), and the fibrogenic particle alpha-quartz. Flow cytometry allowed quantitation of particle binding by measuring increased right angle light scatter (RAS) (TiO2) [40 micrograms/mL], Fe2O3 [100 micrograms/mL], alpha-quartz [200 micrograms/mL], or CAPs [40 micrograms/mL] fold increase RAS: 8.1 +/- 0.9, 4.3 +/- 0.4, 2 +/- 0.1, 1.6 +/- 0.1, respectively). With this quantitative assay, binding of particle was found to be calcium-dependent for TiO2 and Fe2O3 (% inhibition, 61.0 +/- 1.9, 40.0 +/- 5.6, respectively), while alpha-quartz binding was calcium-independent. A panel of polyanionic ligands known to inhibit scavenger-type receptors was used to identify binding mechanisms for environmental particulates. Both heparin and polyinosinic acid (polyI), but not the control polyanion chondroitin sulfate, caused marked inhibition of particulate binding by A549 cells (e.g., TiO2 [40 micrograms/mL] binding; polyI, heparin, and chondroitin sulfate: 73.8 +/- 3.5, 75.5 +/- 6.0, 7.5 +/- 6.7% inhibition, respectively; mean +/- SE, n > or = 4), indicating that scavenger receptor(s), albeit those distinct from the heparin-insensitive acetylated-LDL receptor, mediate particulate binding. The particulates ability to stimulate interleukin (IL-8) production in A549 cells was also tested. alpha-quartz, but not TiO2 or CAPs, caused a dose-dependent production of IL-8 (range 1-6 ng/mL), demonstrating a particle-specific spectrum of epithelial cell cytokine (IL-8) response. The results suggest that lung epithelial cell interaction with environmental particles is mediated by distinct receptors and can lead to particle dependent cytokine responses.
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PMID:Lung epithelial cell (A549) interaction with unopsonized environmental particulates: quantitation of particle-specific binding and IL-8 production. 888 55

We examined the effect of ulinastatin in comparison with prednisolone (PSL) and salazosulfapyridine (SASP), well-known drugs for ulcerative colitis (UC), on two experimental UC models induced by dextran sulfate sodium (DSS) or trinitrobenzene sulfonic acid (TNB) in rats. Ulinastatin at the doses of 3000 approximately 10,000 units/kg/day (i.v.) significantly ameliorated the formation of erosion and infiltration of inflammatory cells in colonic mucosa in DSS-induced rat UC models. Moreover, ulinastatin at the dose of 10,000 units/kg/day (i.v.) significantly suppressed inflammation with ulcer in the colonic mucosa in TNB-induced rat UC models. PSL at the dose of 1 mg/kg/day (p.o.) also was as effective as ulinastatin on the above two UC models, while SASP at the dose of 100 mg/kg/day (p.o.) was less effective than ulinastatin and PSL. In addition, ulinastatin inhibited the activities of elastase and cathepsin G from human leukocytes, and it suppressed TNF alpha, IL-8 and superoxide production by rat macrophages and rabbit leukocytes in vitro. These results suggest that the suppression of inflammatory mediators produced by leukocytes is involved in the mechanism of the anti-UC action of ulinastatin.
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PMID:[Effects of ulinastatin on experimental ulcerative colitis in rats]. 906 98

The epidermal response to 2 different irritants, nonanoic acid (NAA) and sodium lauryl sulfate (SLS), was investigated with 2 different methods. NAA 80% and SLS 4% were applied under occlusion for up to 24 h. Elemental changes were determined in cryosections by x-ray microanalysis. Compared to unexposed skin a significantly higher sodium/potassium ratio was found after 6 h in NAA-exposed skin and a lower ratio in SLS-exposed. At 24 h both substances had induced similar changes, compatible with a cell injury. The findings demonstrate a time-dependent NAA and SLS response. With reverse transcription polymerase chain reaction, the mRNA expression of interleukin-1 alpha (IL-1 alpha), -1 beta (IL-1 beta), -6 (IL-6), and -8 (IL-8), tumor necrosis factor alpha (TNF alpha) and granulocyte macrophage colony stimulating factor (GM-CSF) in shave biopsies from irritated and unexposed skin was studied at 0. 4. 8 and 24 h. NAA, but not SLS, induced an increase in mRNA expression for IL-6 mRNA-expression for GM-CSF was increased after SLS exposure, but not after NAA. These findings indicate a time and substance dependent difference in the up-regulation of mRNA for different cytokines in epidermis during the first 24 h of the irritant reaction. This might be the effect of differences in the irritants action on the cell membranes, which is also reflected by the differences found in the elemental content at 6 h.
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PMID:Different pathways in irritant contact eczema? Early differences in the epidermal elemental content and expression of cytokines after application of 2 different irritants. 911 30

Chemokines are 8-10 kDa proteins involved in the control of leukocyte trafficking and activation. In free solution, chemokines are monomers at physiologic concentrations, although many multimerize at higher concentrations. Cell surface heparan sulfate may sequester chemokines, increasing their local concentrations and facilitating their binding to receptors expressed on leukocytes. In competitive binding assays using immobilized heparin, a 2-3-fold increase in the bound radiolabeled chemokine was seen with increasing concentrations of unlabeled chemokine in the nanomolar range. Unlabeled chemokine concentrations between 0.25 and 50 microM were needed to compete the bound radioactivity. This biphasic competition curve was not seen for N-methyl-L25 IL-8, a variant of IL-8 which is unable to dimerize. In addition, complexes of chemokine and heparin eluted from gel filtration columns with apparent molecular masses of 33-60 kDa, suggesting that chemokine multimerization had occurred. The physiological relevance of this multimerization process was seen from studies using human endothelial cells. The endothelial cell binding sites for IL-8, RANTES, and MCP-1 were deduced to be glycosaminoglycans since competition assays showed the biphasic curves and micromolar IC50 values seen in studies with immobilized heparin, and mRNA for known chemokine receptors was not detected. Furthermore, digestion of endothelial cell monolayers with glycosaminidases decreased chemokine binding by up to 80%. Glycosaminoglycans can act as modulators of the ligand binding affinity of chemokine receptor-bearing cells. Removal of glycosaminoglycans from CHO cells expressing chemokine receptors CXCR1, CCR1, or CCR2 resulted in 40-70% decreases in the binding of RANTES, MCP-1, IL-8, and MIP-1alpha. Our data show that cell surface glycosaminoglycans induce polymerization of chemokines, increasing their local concentration and therefore enhancing their effects on high-affinity receptors within the local microenvironment.
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PMID:Glycosaminoglycans mediate cell surface oligomerization of chemokines. 935 25

Cytokines play a central role in the modulation of the intestinal immune system. They are produced by lymphocytes (especially T cells of the Th1 and Th2 phenotypes), monocytes, intestinal macrophages, granulocytes, epithelial cells, endothelial cells, and fibroblasts. They have proinflammatory functions [interleukin-1 (IL-1), tumor necrosis factor (TNF), IL-6, IL-8, IL-12] or antiinflammatory functions [interleukin-1 receptor antagonist (IL-1ra), IL-4, IL-10, IL-11, transforming growth factor beta (TGF beta)]. Mucosal and systemic concentrations of many pro- and antiinflammatory cytokines are elevated in inflammatory bowel disease (IBD). An imbalance between proinflammatory and antiinflammatory cytokines was found for the IL-1/IL-1ra ratio in the inflamed mucosa of patients with Crohn's disease, ulcerative colitis, diverticulitis, and infectious colitis. Furthermore, the inhibition of proinflammatory cytokines and the supplementations with antiinflammatory cytokines reduced inflammation in animal models, such as the dextran sulfate colitis (DSS) model, the trinitrobenzene sulfonic acid (TNBS) model, or the genetically engineered model of IL-10 knockout mice. Based on these findings a rationale for cytokine treatment was defined. The first clinical trials using neutralizing monoclonal antibodies against TNF alpha (cA2) or the antiinflammatory cytokine IL-10 have shown promising results. However, many questions must be answered before cytokines can be considered standard therapy for IBD.
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PMID:Cytokines in inflammatory bowel disease. 952 21

Endothelium plays a central role in the regulation of site and inflammation specific leukocyte migration. Some of the mediators involved in leukocyte migration, such as chemokines, can bind to heparan sulfate on the endothelium resulting in immobilization near their sites of production. Because CD44 variants expressing V3 have been shown to carry heparan sulfate side chains and to interact through these side chains with heparan sulfate binding growth factors, we investigated the expression of CD44 variants on endothelium. We found a strong expression of V5, V7-8 and V10 CD44 variants and a weaker expression of V3 and V6 CD44 variants on endothelium by using immuno-histochemistry and by FACS analysis. Expression of CD44 V3 variants was confirmed at both the protein and mRNA levels by Western blotting and by reverse transcriptase-PCR respectively. Expression of CD44 variants was unaffected by IL-1beta, IL-8, TNFalpha, IFNgamma or IL-4 treatment, indicating either constitutive expression of these variants or involvement of other cytokines in their regulation.
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PMID:CD44 isoforms, including the CD44 V3 variant, are expressed on endothelium, suggesting a role for CD44 in the immobilization of growth factors and the regulation of the local immune response. 953 3


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