Human keratinocytes constitutively produce but do not process interleukin-18

Br J Dermatol. 2000 Aug;143(2):330-6. doi: 10.1046/j.1365-2133.2000.03759.x.


Background: Interleukin (IL)-18 is a potent immunomodulatory cytokine which promotes T-helper (Th) 1 and cytotoxic responses. IL-18 signals through a two-chain receptor (IL-18R and accessory protein-like subunit, AcPL), and an inhibitory molecule, IL-18 binding protein (IL-18BP), has recently been characterized.

Objectives: The aim of the present study was to define the production of IL-18 and its receptor by human keratinocytes.

Methods: The presence of IL-18 was determined using polymerase chain reaction in human keratinocyte cultures with or without treatment with potential inducers.

Results: The IL-18 gene was constitutively transcribed by primary human keratinocytes and cell lines and was not significantly altered following exposure to IL-1 beta, tumour necrosis factor-alpha, interferon (IFN)-gamma, phorbol myristate acetate or nickel sulphate. IL-18 protein was constitutively present at high levels in keratinocyte lysates and was detectable in supernatants exclusively in the unprocessed, 24-kDa form. Cytokine exposure failed to induce any change in protein levels or processing. Primary keratinocytes produced IL-18R and AcPL constitutively at the mRNA level, in addition to low levels of IL-18BP, which was transcriptionally inducible following treatment with IFN-gamma.

Conclusions: These findings demonstrate that IL-18 is constitutively synthesized by human keratinocytes and is released in an unprocessed form in vitro. Release of IL-18 by human keratinocytes may permit them to regulate IFN-gamma production during cutaneous inflammatory responses and suggests that IL-18 may represent an attractive target for immunomodulatory intervention in Th1-mediated inflammatory diseases such as psoriasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Culture Techniques
  • Cytokines / immunology
  • Gene Expression Regulation
  • Humans
  • Infant, Newborn
  • Interferon-gamma / immunology
  • Interleukin-18 / biosynthesis*
  • Interleukin-18 / genetics
  • Interleukin-18 Receptor alpha Subunit
  • Keratinocytes / immunology
  • Keratinocytes / metabolism*
  • Male
  • RNA, Messenger / genetics
  • Receptors, Interleukin / biosynthesis
  • Receptors, Interleukin / genetics
  • Receptors, Interleukin-18
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription, Genetic
  • Up-Regulation


  • Cytokines
  • IL18R1 protein, human
  • Interleukin-18
  • Interleukin-18 Receptor alpha Subunit
  • RNA, Messenger
  • Receptors, Interleukin
  • Receptors, Interleukin-18
  • Interferon-gamma