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)

The chemokine RANTES is a chemoattractant for eosinophils, T lymphocytes of memory phenotype and monocytes, suggesting that it plays an important part in chronic inflammatory and allergic diseases. In various types of cells, RANTES production is markedly induced by tumour necrosis factor (TNF)-alpha and interferon (IFN)-gamma in combination. Psoriasis vulgaris is a chronic cutaneous inflammatory disease. Cytokines and chemokines produced by T cells and epidermal keratinocytes, such as interleukin (IL) 8, are involved in the pathogenesis of psoriasis. T-cell clones obtained from psoriatic skin have been shown to produce the Th1 cytokine IFN-gamma. In addition, abnormal expression of proinflammatory cytokines including TNF-alpha has been observed in psoriatic lesions. These reports led us to hypothesis that psoriatic skin could provide epidermal keratinocytes with TNF-alpha and IFN-gamma, so that keratinocytes could produce RANTES. In this study, we addressed the question as to whether RANTES was involved in psoriasis vulgaris. Immunohistochemistry of skin biopsies showed RANTES was present in the intercellular spaces between epidermal keratinocytes, in the fully developed lesions from the middle to the edge of psoriatic plaques, but not in the perilesional uninvolved and healthy control skin. Further, we confirmed the production of RANTES, together with IL-8, by cultured normal human epidermal keratinocytes, using an enzyme-linked immunosorbent assay. Stimulation with TNF-alpha and IFN-gamma in combination synergistically increased the RANTES production in this system. These results clearly demonstrate the expression of RANTES in psoriatic lesions and suggest the involvement of this chemokine in the outcome of cutaneous inflammatory diseases. Tacalcitol (1 alpha,24(R)-dihydroxyvitamin D3), an active vitamin D3 analogue, inhibited RANTES and IL-8 production in cultured normal epidermal keratinocytes. This result indicates that active vitamin D3 is effective in the regulation of chemokine production by epidermal keratinocytes, which may partly account for its action as an antipsoriatic drug.
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PMID:RANTES expression in psoriatic skin, and regulation of RANTES and IL-8 production in cultured epidermal keratinocytes by active vitamin D3 (tacalcitol). 953 24

1. The production of chemokines, RANTES and IL-8 in cultured human dermal fibroblasts and the effects of tacalcitol (1alpha,24(R)-dihydroxyvitamin D3) were studied using an enzyme-linked immunosorbent assay. 2. In the unstimulated condition, RANTES and IL-8 were at a trace level in the culture supernatant. On stimulation with TNF-alpha alone for 24 h, RANTES and IL-8 production were induced. Tacalcitol suppressed RANTES and IL-8 production dose-dependently at concentrations between 10(-12) M and 10(-7) M. 3. When the cells were treated with TNF-alpha and IFN-gamma in combination, RANTES production was enhanced, but IL-8 production was not changed, compared to TNF-alpha-treated cells. Tacalcitol decreased IL-8 production dose-dependently as observed in the TNF-alpha-treated cells. On the other hand, RANTES production was enhanced by 10(-11) M and 10(-10) M of tacalcitol, and dose-dependently suppressed by tacalcitol concentrations higher than 10(-9) M. 4. Active vitamin D3 compounds, betamethasone valerate and cyclosporin A were compared with respect to their effects on chemokine production. Three active vitamin D3 compounds, tacalcitol, 1alpha,25-dihydroxyvitamin D3 and MC903 (calcipotriol), inhibited the production of RANTES and IL-8, with very similar potencies. Betamethasone valerate also inhibited these chemokine productions, but with greater potency than active vitamin D3 compounds. Cyclosporin A significantly stimulated RANTES production at 10(-6) M and IL-8 production at 10(-7) M and 10(-6) M. 5. The results of this study suggest that active vitamin D3 compounds exert some beneficial effects in the treatment of inflammatory skin diseases via regulation of the production of chemokines by dermal fibroblasts.
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PMID:Regulation of RANTES and IL-8 production in normal human dermal fibroblasts by active vitamin D3 (tacalcitol). 972 55