Differential Gene Induction of Human Beta-Defensins (hBD-1, -2, -3, and -4) in Keratinocytes Is Inhibited by Retinoic Acid

J Invest Dermatol. 2004 Sep;123(3):522-9. doi: 10.1111/j.0022-202X.2004.23234.x.


Human skin is able to mount a fast response against invading harmful bacteria through the rapid production of inducible peptide antibiotics such as the human beta-defensins (hBD). To gain more insight into the role and regulation of inducible beta-defensins in the innate immunity of human skin, we investigated whether gene induction of the human beta-defensins hBD-1, -2, -3, and -4 in keratinocytes is regulated in a similar manner. Therefore, we performed a comparative study of gene expression of these four hBD in primary cultured keratinocytes using real-time PCR. A basal mRNA expression was observed for all four hBD in primary keratinocytes, which strongly increased for hBD-2, -3, and -4 during Ca(2+)-induced differentiation of the keratinocytes. This effect was completely abolished when the keratinocytes were pre-treated with all-trans-retinoic acid (RA). Furthermore, the differential induction of hBD-2, -3, and -4 gene expression in keratinocytes by proinflammatory cytokines, phorbol-myristate-acetate (PMA), and bacteria was inhibited by more than 90% when the keratinocytes were pre-incubated with RA. Inhibition of IL-1beta-mediated hBD-2 induction through RA was further confirmed by gene reporter assays and western-blot analysis. We conclude that RA is a potent inhibitor of beta-defensin induction in keratinocytes and might downregulate the inducible innate chemical defense system of human skin.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Calcium / pharmacology
  • Carcinogens / pharmacology
  • Cells, Cultured
  • Gene Expression Regulation / drug effects
  • Humans
  • Interferon-gamma / pharmacology
  • Interleukin-1 / pharmacology
  • Keratinocytes / cytology
  • Keratinocytes / physiology*
  • Pseudomonas Infections / physiopathology
  • Pseudomonas aeruginosa
  • RNA, Messenger / analysis
  • Tetradecanoylphorbol Acetate / pharmacology
  • Transcriptional Activation
  • Tretinoin / pharmacology*
  • Tumor Necrosis Factor-alpha / pharmacology
  • Up-Regulation
  • beta-Defensins / genetics*


  • Antineoplastic Agents
  • Carcinogens
  • DEFB1 protein, human
  • DEFB103A protein, human
  • DEFB4A protein, human
  • Interleukin-1
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • beta-Defensins
  • Tretinoin
  • Interferon-gamma
  • Tetradecanoylphorbol Acetate
  • Calcium