Abstract
Background
Interleukin (IL)-33 is a dual functional, IL-1 family member cytokine, whose exact
roles in inflammatory skin diseases are still unknown. IL-17A is a key cytokine in
the pathogenesis of psoriasis.
Objectives
We investigated if IL-17A could induce IL-33 in epidermal keratinocytes, and the signaling
mechanisms involved.
Methods
IL-33 levels were evaluated by RT-PCR and western blot in human keratinocytes following
IL-17A simulation. IL-33 immunohistochemical staining of psoriatic skin samples was
also performed and compared with that of control tissues. The role of signaling pathways
downstream of IL-17A was investigated using small molecule inhibitors of EGFR, ERK,
p38, and JAK. Adenovirus vector expressing dominant negative STAT1 was also utilized.
Results
IL-33 and its receptor, ST2L, were expressed in the psoriatic epidermis, and the associated
infiltrating cells. IL-17A induced IL-33 expression at mRNA and protein levels in
a time- and concentration-dependent manner. IL-17A caused phosphorylation of EGFR,
ERK, p38, and STAT1. IL-17A-induced IL-33 expression was blocked by the addition of
EGFR, ERK, p38, and JAK inhibitors, and dominant negative STAT1-expressing adenovirus
vector.
Conclusion
IL-17A induced IL-33 in NHEKs through EGFR, ERK, p38, and JAK/STAT1 pathways, which
were necessary for the induction of IL-33. IL-33, induced by IL-17A in epidermal keratinocytes,
may be involved in the pathophysiology of inflammatory skin diseases, including psoriasis.
Keywords
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Article info
Publication history
Published online: June 13, 2013
Accepted:
April 11,
2013
Received in revised form:
April 8,
2013
Received:
October 19,
2012
Identification
Copyright
© 2013 Japanese Society for Investigative Dermatology. Published by Elsevier Inc. All rights reserved.
