Interferon-Gamma-Induced RANTES Production by Human Keratinocytes Is Enhanced by IL-1β, TNF-α, IL-4 and IL-13 and Is Inhibited by Dexamethasone and Tacrolimus

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Abstract
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-γ (100 ng/ml) or IL-1β (100 ng/ml) significantly induced RANTES production by KCs in 48-hour culture. These cytokines synergistically increased RANTES production by KCs. TNF-α (100 ng/ml), IL-4 (100 ng/ml) or IL-13 (100 ng/ml) markedly enhanced the RANTES production by KCs induced by IFN-γ (100 ng/ml) although none of those cytokines significantly enhanced that induced by IL-1β (100 ng/ml) in 48-hour culture. Dexamethasone (10–8 M) strongly inhibited RANTES production by KCs induced by the combination of IFN-γ 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-γ, IL-1β, TNF-α, IL-4 and IL-13, and can be modulated by immunosuppressive drugs. Our data suggest that RANTES is involved in skin inflammation.