Interleukin-1: a key inflammatory mediator in psoriasis?
The pro-inflammatory cytokine interleukin-1 (IL-1) is constitutively expressed by keratinocytes in vivo and has been shown to be expressed in psoriatic lesional skin. To determine what role the IL-1 system might contribute to the inflammatory process in psoriasis, semi-quantitative RT-PCR and cRNA microarray studies were performed on biopsies excised from lesional and non-lesional skin. Whilst IL-1alpha mRNA levels showed a reduction in lesional skin in a subset of patients, steady state IL-1beta mRNA was increased markedly. Neither of the two IL-1 receptor transcripts nor total IL-1 receptor antagonist exhibited major changes within the lesion. Expression of the IL-1-induced chemokine IL-8 was only observed in lesional epidermis. Functional genomic experiments comparing transcriptome profiles derived from psoriatic lesional skin and IL-1 stimulated keratinocytes demonstrated a striking level of overlap. Taken together, these data suggest that IL-1 is likely to be an important mediator in the initiation and maintenance of psoriatic plaques and may represent an attractive therapeutic target.
Mee
John B
JB
St John's Institute of Dermatology, King's College London, St Thomas' Hospital, Lambeth Palace Road, London SE1 7EH, UK. john.mee@kcl.ac.uk
Cork
Michael J
MJ
di Giovine
Francesco S
FS
Duff
Gordon W
GW
Groves
Richard W
RW
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002478:Cells, Cultured; D000078404:Epidermal Cells; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism*; D007375:Interleukin-1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011565:Psoriasis / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D012333:RNA, Messenger; D012867:Skin / Q000378:metabolism / Q000473:pathology*
D018836:Inflammation Mediators; D007375:Interleukin-1; D016209:Interleukin-8; D012333:RNA, Messenger