Human keratinocytes constitutively produce but do not process interleukin-18.
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.[1]References
- Human keratinocytes constitutively produce but do not process interleukin-18. Mee, J.B., Alam, Y., Groves, R.W. Br. J. Dermatol. (2000) [Pubmed]
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