Interferon-gamma-induced RANTES production by human keratinocytes is enhanced by IL-1beta, TNF-alpha, IL-4 and IL-13 and is inhibited by dexamethasone and tacrolimus

BACKGROUND AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.