Effect of calcitriol on growth, differentiation, chemokine mRNA expression of cultured keratinocytes and on keratinocyte-T cell binding.

P de Haan, S Sampat, E M van der Raaij, I Bruynzeel, D M Boorsma, R Willemze, T J Stoof
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Abstract

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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骨化三醇对体外培养角质形成细胞生长、分化、趋化因子mRNA表达及角质形成细胞- t细胞结合的影响。
骨化三醇最近被证明对牛皮癣有效。然而,它的作用方式并不完全清楚。本研究主要研究骨化三醇对角质形成细胞(KC)生长、分化、趋化因子mRNA和ICAM-1 mRNA表达的影响,以及对t细胞与角质形成细胞结合的影响。体外实验表明骨化三醇具有较强的抗增殖作用和诱导终末分化作用。γ - ifn诱导γ - ip -10和ICAM-1 mRNA表达,不受骨化三醇的影响。此外,通过细胞粘附实验测量,ICAM-1在KC细胞表面的功能表达也没有受到影响。IL-8和huGRO mrna在KC中组成性产生,经环己亚胺孵育后证实。骨化三醇对IL-1 α上调IL-8和huGRO mRNA也没有影响。由此得出结论,骨化三醇具有很强的抗增殖活性,不会干扰KC对γ - ifn和il - α诱导的趋化因子表达的反应性,也不会干扰t细胞与角质形成细胞的粘附。
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