Wakugawa M, Nakamura K, Akatsuka M, Nakagawa H, Tamaki K
Department of Dermatology, Faculty of Medicine, University of Tokyo, Tokyo, Japan.
Dermatology. 2001;202(3):239-45. doi: 10.1159/000051644.
Recent studies have shown that RANTES plays a role in the pathogenesis of inflammatory skin diseases. We examined the production of RANTES by human keratinocytes (KCs) when cultured with various cytokines.
IFN-gamma (100 ng/ml) or IL-1beta (100 ng/ml) significantly induced RANTES production by KCs in 48-hour culture. These cytokines synergistically increased RANTES production by KCs. TNF-alpha (100 ng/ml), IL-4 (100 ng/ml) or IL-13 (100 ng/ml) markedly enhanced the RANTES production by KCs induced by IFN-gamma (100 ng/ml) although none of those cytokines significantly enhanced that induced by IL-1beta (100 ng/ml) in 48-hour culture. Dexamethasone (10(-8) M) strongly inhibited RANTES production by KCs induced by the combination of IFN-gamma and IL-4, while tacrolimus (FK-506, 10(-8) and 10(-6) M) showed partial inhibition.
These results revealed that RANTES production by KCs is regulated by inflammatory cytokines, such as IFN-gamma, IL-1beta, TNF-alpha, IL-4 and IL-13, and can be modulated by immunosuppressive drugs. Our data suggest that RANTES is involved in skin inflammation.
近期研究表明，RANTES在炎症性皮肤病的发病机制中起作用。我们检测了人角质形成细胞（KCs）在与多种细胞因子共培养时RANTES的产生情况。
在48小时培养中，干扰素-γ（100 ng/ml）或白细胞介素-1β（100 ng/ml）显著诱导KCs产生RANTES。这些细胞因子协同增加KCs产生RANTES。肿瘤坏死因子-α（100 ng/ml）、白细胞介素-4（100 ng/ml）或白细胞介素-13（100 ng/ml）显著增强干扰素-γ（100 ng/ml）诱导的KCs产生RANTES，尽管在48小时培养中这些细胞因子均未显著增强白细胞介素-1β（100 ng/ml）诱导的RANTES产生。地塞米松（10⁻⁸ M）强烈抑制干扰素-γ和白细胞介素-4联合诱导的KCs产生RANTES，而他克莫司（FK-506，10⁻⁸和10⁻⁶ M）表现出部分抑制作用。
这些结果表明，KCs产生RANTES受干扰素-γ、白细胞介素-1β、肿瘤坏死因子-α、白细胞介素-4和白细胞介素-13等炎性细胞因子调节，并可被免疫抑制药物调节。我们的数据提示RANTES参与皮肤炎症。
