Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P10145 (IL-8)
 23,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Calcitriol has recently been shown to be effective against psoriasis. However, its mode of action is not exactly known. The present study focused on the influence of calcitriol on growth, differentiation, chemokine mRNA and ICAM-1 mRNA expression of keratinocytes (KC) and on the binding of T-cells to keratinocytes. In vitro studies showed that calcitriol has a strong anti-proliferative effect and induces terminal differentiation. gamma-IP-10 and ICAM-1 mRNA were induced by gamma-IFN, an induction not influenced by calcitriol. Moreover, the functional expression of ICAM-1 on the KC cell surface as measured by a cell adhesion assay, was not influenced either. IL-8 and huGRO mRNAs were constitutively produced in KC, as was demonstrated after incubation with cycloheximide. Up-regulation of both IL-8 and huGRO mRNA by IL-1 alpha was also not affected by calcitriol. It is concluded that calcitriol has a strong antiproliferative activity and does not interfere with KC responsiveness to gamma-IFN and IL-alpha induced chemokine expression or with the adhesion of T-cells to keratinocytes.
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PMID:Effect of calcitriol on growth, differentiation, chemokine mRNA expression of cultured keratinocytes and on keratinocyte-T cell binding. 807 37

IL-8, a potent chemotactic factor for neutrophil granulocytes and lymphocytes, is a proinflammatory cytokine secreted by a variety of cell types, including T cells. Stimulation of the CD28 cell surface molecule delivers costimulatory signals essential for lymphokine production in activated T cells via a conserved sequence element found in the promoter of several lymphokine genes. Anti-CD28-stimulated T cells produced significant amounts of IL-8; additionally, costimulation with anti-CD3 and anti-CD28 Abs resulted in a synergistic induction of IL-8 secretion. Sequence homology, single nucleotide mutations, and anti-CD28 Ab stimulation studies established that the NF-kappa B-like sequence in the promoter of the IL-8 gene functioned as a CD28 response element. Furthermore, cyclosporin A, but not rapamycin, blocked the synergistic induction of IL-8 expression achieved with anti-CD3 and anti-CD28 costimulation. The involvement of a CD28 response element in the induction of IL-8 expression in activated T cells may provide new insights into the pathogenesis and persistence of immune disorders characterized by increased levels of IL-8, such as psoriasis and rheumatoid arthritis.
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PMID:Induction of IL-8 expression in T cells uses the CD28 costimulatory pathway. 807 62

Interleukin-8 is assumed to play a central role in the pathogenesis of psoriasis. Since an increased expression of the interleukin-8 receptor has been observed both in polymorphonuclear leukocytes and in affected psoriatic epidermis, we were interested in whether the interleukin-8 receptor could be a molecular target of antipsoriatic compounds. Cyclosporine, calcitriol, calcipotriol or dithranol caused a dose-dependent decrease in interleukin-8 binding to cultured human keratinocytes, while interleukin-8 binding to granulocytes was not affected. In addition, the interleukin-8-induced human leukocyte antigen-DR (HLA-DR) expression of keratinocytes was nearly completely blocked by treatment of the cells with these substances. The inhibition of the keratinocyte interleukin-8 receptor and its function by antipsoriatic drugs may contribute to their therapeutic action.
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PMID:The interleukin-8 receptor: a potential target for antipsoriatic therapy? 808 60

A significant proportion of the infiltrating cells in several inflammatory skin diseases, including psoriasis and allergic contact dermatitis, are monocytes. Additionally, it is known that the cytokine monocyte chemotactic and activating factor (MCAF) can be produced by several cell types present in the skin, suggesting a significant role for MCAF in the accumulation of monocytes during immunological and inflammatory skin reactions. We have recently developed a precise method for quantification of the amount of a specific mRNA species in a given sample and have used this technique to compare specific MCAF mRNA amounts in cultures of human keratinocytes, dermal fibroblasts, endothelial cells, and monocytes, after stimulation with interleukin 1 alpha (IL-1 alpha) for 6 h. Endothelial cells produced very high, monocytes and fibroblasts intermediate, and keratinocytes low amounts of MCAF mRNA. We have also performed time course studies of MCAF mRNA levels in the four cell types. Our findings suggest that the regulation of MCAF mRNA expression in these cells parallels the regulation of the lymphocyte and neutrophil chemotactic factor interleukin 8.
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PMID:Expression of monocyte chemotactic and activating factor (MCAF) in skin related cells. A comparative study. 814 9

The immunosuppressive peptide cyclosporin A (CyA) is an extremely effective therapy for severe recalcitrant psoriasis, although its mechanism of action is unknown. In this study, we examined the effect of CyA on keratinocyte growth and cytokine expression, and showed that CyA inhibits the growth of murine and human keratinocytes (KC) and KC cell lines. In addition, CyA inhibits the expression of cytokine genes in a dose-dependent fashion. After 2 days' incubation with 20 microM CyA, interleukin-1 alpha (IL-1 alpha), interleukin-1 beta (IL-1 beta), and interleukin 8 (IL-8) mRNA were decreased by 4-fold, 3.3-fold and 3.3-fold, respectively, in COLO-16, a keratinocyte cell line. IL-1 biological activity recovered from COLO-16 culture supernatants decreased to one-fifth of that of controls. In the murine KC cell line PAM 212, 10 microM CyA treatment for 2 days downregulated IL-1 alpha, tumour necrosis factor-alpha (TNF-alpha) and IL-1 receptor by 60%, but had no effect on the message for interleukin 3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), ornithine decarboxylase and beta-actin. Cells cultured for 5 days in the presence of CyA required much lower concentrations (2 microM) to achieve the same degree of inhibition of IL-1 alpha. Similar tissue concentrations of CyA have been reported in psoriatics undergoing CyA therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cyclosporin A inhibits keratinocyte cytokine gene expression. 814 71

Psoralen plus UV-A (PUVA) is an effective therapy for psoriasis but also for other inflammatory dermatoses. The precise mechanisms of action, however, are not absolutely clear. Therefore, the effect of PUVA on the release of the proinflammatory cytokines interleukin (IL)-1, IL-6, IL-8 and tumor necrosis factor alpha (TNF alpha) was studied. Peripheral blood mononuclear cells (PBMC) obtained from humans were incubated with 8-methoxypsoralen (8-MOP) and exposed to UV-A (20 kJ/m2). This treatment resulted in a significant reduction of IL-6 and IL-8 amounts in the supernatants. In addition, an inhibition of IL-1 beta and TNF alpha production by lipopolysaccharide (LPS)-stimulated PBMC was observed upon PUVA treatment. Accordingly, northern blot analysis showed decreased levels of mRNA encoding for IL-1 beta, IL-6, IL-8 and TNF alpha in PUVA-treated PBMC. Finally PBMC were obtained from psoriatics undergoing oral photochemotherapy before the beginning and after completion of treatment. The PBMC collected after PUVA spontaneously produced significantly less IL-6 and IL-8 in comparison to the respective samples obtained before therapy. A similar suppression of IL-1 beta and TNF alpha by in vivo PUVA was found in LPS-stimulated PBMC. The present data demonstrate that PUVA both in vitro and in vivo suppresses the production of the proinflammatory cytokines IL-1 beta, IL-6, IL-8 and TNF alpha by PBMC. Because these cytokines are important in the mediation of inflammatory reactions, one may speculate that the inhibitory effects could contribute to the antiinflammatory activity of PUVA.
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PMID:Cytokine release by peripheral blood mononuclear cells is affected by 8-methoxypsoralen plus UV-A. 816 38

Pro-inflammatory cytokines mediate their biological functions after they are secreted or released from intracellular to extracellular milieu. Keratinocytes have proven to be able to produce various cytokines including IL-1 and IL-8. Dysregulations of IL-1 and IL-8 were found in psoriatic lesions. Recently, vitamin D3 (VD3) was found to be an effective and safe therapy for psoriasis. In the present study, we investigated the effects of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) and its analogue MC903 on IL-1 alpha and IL-8 secretion by human keratinocytes in vitro. Cultured normal human keratinocytes (NHKs) produced considerable amounts of IL-1 alpha but secreted less. In contrast, they produced less IL-8 and almost all molecules were secreted to the culture supernatants. Treatment of unstimulated NHKs with 1,25(OH)2D3 or MC903 showed little effects on IL-1 alpha production and secretion though they slightly enhanced IL-8. When NHKs were stimulated with tumour necrosis factor-alpha (TNF alpha), both IL-1 alpha and IL-8 secretions were enhanced and these enhancements were inhibited by 1,25(OH)2D3 or MC903. Stimulation of NHKs with phorbol 12-myristate 13-acetate(PMA) and lipopolysaccharide(LPS) resulted in an increase of IL-8 and decrease of IL-1 alpha in the culture supernatants. Addition of 1,25(OH)2D3 or MC903 inhibited the increased secretion of IL-8 but restored decreased secretion of IL-1 alpha from stimulated NHKs dose dependently. Hydrocortisone and cyclosporin A showed similar inhibitory effects on PMA/LPS-increased IL-8 secretion from NHKs but had little effect of restoring IL-1 alpha.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regulatory effects of 1,25-dihydroxyvitamin D3 and a novel vitamin D3 analogue MC903 on secretion of interleukin-1 alpha (IL-1 alpha) and IL-8 by normal human keratinocytes and a human squamous cell carcinoma cell line (HSC-1). 819 81

In human fibroblast cultures TPA increased IL-6 and IL-8 production. This was reduced by vitamin D3 metabolites and analogs. The two analogs employed: 1,25 (OH)2-22 (E)-dehydro-24-monohomo vitamin D3 (Compound A) and 1,25 (OH)2 -22 (E)-dehydro-24 dihomo-vitamin D3 (Compound B) may be useful in the therapy of pathologic proliferative disorders including psoriasis, particularly since they are less toxic and have less effect on calcium metabolism than vitamin D3.
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PMID:Inhibition of IL-6 and IL-8 production in human fibroblast cell lines by 1,25 (OH)2 vitamin D3 and two of its analogs with lower calcemic activity. 820 27

The purpose of this study was to investigate and to compare, by in situ hybridization, gene expression of IL-1 beta, IL-8, TGF-beta 1, TGF-beta 2, TGF-beta 3, TGF-alpha, p53 and c-myc in lesions and in non-involved skin of patients with psoriasis. All lesional skin biopsies showed overexpression of IL-1 beta, IL-8 TGF-alpha mRNAs. IL-1 beta hybridization signals were strong in a small number of cells localized predominantly in the dermal papillae and in the suprapapillary epidermis. Overexpression of TGF-alpha was observed in all suprabasal keratinocytes, whereas strongly elevated IL-8 mRNA expression was found to be restricted to clusters of suprabasal keratinocytes. TGF-beta 3, p53 and c-myc transcripts were clearly detected in the epidermis of all biopsies, although expression levels were comparable in lesional and non-lesional skin.
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PMID:In situ hybridization analysis of cytokine, proto-oncogene and tumour suppressor gene expression in psoriasis. 821 83

Interleukin (IL)-8 is a member of the supergene family of proinflammatory and chemotactic cytokines recently termed chemokines. IL-8 has been implicated in the pathogenesis of inflammatory skin diseases such as psoriasis. In this study, IL-8 mRNA expression and protein production were determined in normal cultured human epidermal keratinocytes after ultraviolet-B (UVB) irradiation. Messenger RNA levels were determined by the reverse transcriptase-polymerase chain reaction (RT-PCR) method. Total RNA was extracted from cultured keratinocytes at various time points post-irradiation, reverse transcribed to cDNA, and amplified by PCR using a labeled specific primer for the target gene. Amplified products were sized by electrophoresis, visualized by autoradiography, and quantitated by densitometry. Autoradiographs were normalized relative to glyceraldehyde-3-phosphate-dehydrogenase (G3PDH) signals. Constitutive expression of IL-8 mRNA was seen in normal cultured keratinocytes. After 100 or 300 J/m2 UVB irradiation, a rapid increase in IL-8 mRNA level was observed within 1 h after irradiation. At 24 h after irradiation, the mRNA level was elevated 11-13 times compared with the control level. Production of IL-8 protein in culture supernatants was assayed by enzyme-linked immunosorbent assay (ELISA). Significant levels of IL-8 protein were observed at 24 h after irradiation. Cycloheximide treatment blocked this IL-8 protein induction. As IL-8 is known to be an inflammatory cell chemotactic factor, these results suggest a possible role for IL-8 in UVB-induced skin inflammation and diseases.
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PMID:IL-8 gene expression and production in human keratinocytes and their modulation by UVB. 822 30


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