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.
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.
Authors: Shalaka S Hampras; Mary Nesline; Paul K Wallace; Kunle Odunsi; Nicholas Furlani; Warren Davis; Kirsten B Moysich Journal: J Cancer Epidemiol Date: 2012-08-26