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

Dermatology. 2001;202(3):239-45. doi: 10.1159/000051644.

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-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Inflammatory Agents / pharmacology
  • Cells, Cultured
  • Chemokine CCL5 / biosynthesis*
  • Cytokines / pharmacology*
  • Dexamethasone / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • Humans
  • Immunosuppressive Agents / pharmacology
  • Interferon-gamma / pharmacology
  • Interleukin-1 / pharmacology
  • Interleukin-13 / pharmacology
  • Interleukin-4 / pharmacology
  • Keratinocytes / cytology
  • Keratinocytes / drug effects*
  • Keratinocytes / metabolism
  • Tacrolimus / pharmacology*
  • Tumor Necrosis Factor-alpha / pharmacology
  • Up-Regulation

Substances

  • Anti-Inflammatory Agents
  • Chemokine CCL5
  • Cytokines
  • Immunosuppressive Agents
  • Interleukin-1
  • Interleukin-13
  • Tumor Necrosis Factor-alpha
  • Interleukin-4
  • Dexamethasone
  • Interferon-gamma
  • Tacrolimus