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Human keratinocytes constitutively produce but do not process interleukin‐18
Author(s) -
Mee J.B.,
Alam Y.,
Groves R.W.
Publication year - 2000
Publication title -
british journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.304
H-Index - 179
eISSN - 1365-2133
pISSN - 0007-0963
DOI - 10.1046/j.1365-2133.2000.03759.x
Subject(s) - keratinocyte , cytokine , receptor , biology , microbiology and biotechnology , interferon gamma , tumor necrosis factor alpha , interleukin , alpha chain , interleukin 20 , in vitro , immunology , interleukin 5 , biochemistry
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‐1β, tumour necrosis factor‐α, interferon (IFN)‐γ, 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‐γ. 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‐γ 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.