Abstract
Background
Ketoprofen (KP) is a widely used nonsteroidal anti-inflammatory drug that inhibits
prostaglandin biosynthesis. We have previously shown that topical KP treatment at
the sensitizing site inhibits the development of contact hypersensitivity (CHS) to
picryl chloride (PCl).
Objective
We investigated the mechanism underlying the KP-induced immunosuppression of CHS by
application of KP.
Methods
We analyzed the CHS responses to the non-sensitizing site and subsequent sensitization
with PCl, and by transfer of the draining lymph node cells (LNCs) from KP-tolerated
mice to recipient mice. Changes in the Foxp3 expression of LNCs from KP-phototreated
skin were also examined by real-time PCR.
Results
Topical application of KP to not only the sensitizing but also non-sensitizing site
suppressed CHS response. The immunosuppression was transferred with LNCs from mice
treated with PCl plus KP, but not from mice treated oxazolone plus KP. In this transfer
study, the CD4+ CD25+ subset of LNCs exerted the suppressive effect, while CD25+ cell-depleted LNCs lost the inhibitory ability. CTLA-4 blocking with a specific antibody,
but not IL-10 blocking, abrogated the activity of CD4+ CD25+ cells. Moreover, Foxp3 mRNA expression was remarkably increased in LNCs from PCl
and KP-treated mice.
Conclusion
The immunosuppression of CHS by topical application of KP is systemic and haptein-specific.
Treg cells play an important role in the suppressive effect by KP.
Keywords
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Article info
Publication history
Published online: July 12, 2010
Accepted:
October 30,
2008
Received in revised form:
October 28,
2008
Received:
June 26,
2008
Identification
Copyright
© 2008 Japanese Society for Investigative Dermatology. Published by Elsevier Inc. All rights reserved.
