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.


OBJECTIVE
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.
Mee
J B
JB
University College London Centre for Dermatology, Jules Thorn Institute, Middlesex Hospital, Mortimer Street, London W1T 3AA, UK. j.mee@ucl.ac.uk
Alam
Y
Y
Groves
R W
RW
D018929:Cell Culture Techniques; D016207:Cytokines / Q000276:immunology; D005786:Gene Expression Regulation; D006801:Humans; D007231:Infant, Newborn; D007371:Interferon-gamma / Q000276:immunology; D020382:Interleukin-18 / Q000096:biosynthesis* / Q000235:genetics; D053727:Interleukin-18 Receptor alpha Subunit; D015603:Keratinocytes / Q000276:immunology / Q000378:metabolism*; D008297:Male; D012333:RNA, Messenger / Q000235:genetics; D018123:Receptors, Interleukin / Q000096:biosynthesis / Q000235:genetics; D053724:Receptors, Interleukin-18; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic; D015854:Up-Regulation
D016207:Cytokines; C508572:IL18R1 protein, human; D020382:Interleukin-18; D053727:Interleukin-18 Receptor alpha Subunit; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D053724:Receptors, Interleukin-18; D007371:Interferon-gamma