Human keratinocytes constitutively express interleukin-18 and secrete biologically active interleukin-18 after treatment with pro-inflammatory mediators and dinitrochlorobenzene

J Invest Dermatol. 1999 Nov;113(5):766-72. doi: 10.1046/j.1523-1747.1999.00750.x.


Interleukin-18 is a potent inducer of interferon-gamma by activated T cells, macrophages, and monocytes and is synthesized as an inactive precursor. Pro-interleukin-18 must be cleaved by interleukin-1-beta-converting enzyme for secretion of the biologically active form. We report that among selected non-bone marrow derived skin cells, interleukin-18 mRNA is constitutively expressed by human keratinocytes and not by dermal microvascular endothelial cells, dermal fibroblasts, or melanocytes. Interleukin-18 mRNA and intracellular protein levels are neither changed in human keratinocytes nor induced in human dermal microvascular endothelial cells, dermal fibroblasts, or melanocytes by exposure to pro-inflammatory stimuli. Exposure of human keratinocytes to phorbol 12-myrisate 13-acetate, lipopolysaccharides or the contact sensitizer DNCB results in the secretion of immunoprecipitable interleukin-18 protein. Human keratinocyte-secreted interleukin-18 is biologically active, in that conditioned media from phorbol 12-myrisate 13-acetate, lipopolysaccharide and DNCB-treated human keratinocytes induce interferon-gamma expression by peripheral blood mononuclear cells. This bioactivity is neutralized by anti-interleukin-18, but not anti-interleukin-12 antibodies. By immunohistochemistry, interleukin-18 protein is detected in basal keratinocytes of normal human skin, but its expression is markedly upregulated in suprabasal keratinocytes in psoriasis. These findings indicate that human keratinocytes are a source of biologically functional interleukin-18 and thus are capable of playing an initiating part in the local interferon-gamma-dependent inflammatory processes through expression, activation, and secretion of interleukin-18.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Dinitrochlorobenzene / pharmacology*
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / metabolism
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Humans
  • Immunohistochemistry
  • Inflammation Mediators / pharmacology*
  • Interferon-gamma / pharmacology
  • Interleukin-18 / genetics*
  • Interleukin-18 / metabolism
  • Keratinocytes / drug effects*
  • Keratinocytes / metabolism*
  • Lipopolysaccharides / pharmacology
  • Melanocytes / drug effects
  • Melanocytes / metabolism
  • Psoriasis / metabolism
  • RNA, Messenger / metabolism
  • Skin / chemistry
  • T-Lymphocytes / physiology
  • Tetradecanoylphorbol Acetate / pharmacology


  • Dinitrochlorobenzene
  • Inflammation Mediators
  • Interleukin-18
  • Lipopolysaccharides
  • RNA, Messenger
  • Interferon-gamma
  • Tetradecanoylphorbol Acetate