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.
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.
Wakugawa
M
M
Department of Dermatology, Faculty of Medicine, University of Tokyo, Tokyo, Japan. wakugawa-tky@umin.ac.jp
Nakamura
K
K
Akatsuka
M
M
Nakagawa
H
H
Tamaki
K
K
D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002478:Cells, Cultured; D018946:Chemokine CCL5 / Q000096:biosynthesis*; D016207:Cytokines / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D018793:Interleukin-13 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016559:Tacrolimus / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015854:Up-Regulation
D000893:Anti-Inflammatory Agents; D018946:Chemokine CCL5; D016207:Cytokines; D007166:Immunosuppressive Agents; D007375:Interleukin-1; D018793:Interleukin-13; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D003907:Dexamethasone; D007371:Interferon-gamma; D016559:Tacrolimus