Publication Date:
2012-09-15
Description:
Glycogen synthase kinase-3 (GSK-3) facilitates interferon (IFN)- signaling. Because IFN- is involved in inflammatory skin diseases, such as psoriasis, the aim of this study was to investigate the pathogenic role of GSK-3 in 12- O -tetradecanoylphorbol-13-acetate (TPA)-induced IFN--mediated ear skin inflammation. TPA (3 μg per ear) induced acute skin inflammation in the ears of C57BL/6 mice, including edema, infiltration of granulocytes but not T cells, and IFN- receptor 1-mediated deregulation of intercellular adhesion molecule 1 (CD54). TPA/IFN- induced GSK-3 activation, which in turn activated signal transducer and activator of transcription 1. Inhibiting GSK-3 pharmacologically, by administering 6-bromoindirubin-3'-oxime (1.5 μg per ear), and genetically, with lentiviral-based short-hairpin RNA, reduced TPA-induced acute skin inflammation but not T-cell infiltration. It is noteworthy that inhibiting GSK-3 decreased TPA-induced IFN- production and the nuclear translocation of T-box transcription factor Tbx21, a transcription factor of IFN-, in CD3-positive T cells. In chronic TPA-induced skin inflammation, inhibiting GSK-3 attenuated epidermis hyperproliferation and dermis angiogenesis. These results demonstrate the dual role of GSK-3 in TPA-induced skin inflammation that is not only to facilitate IFN- signaling but also to regulate IFN- production. Inhibiting GSK-3 may be a potential treatment strategy for preventing such effects.
Print ISSN:
0022-3565
Electronic ISSN:
1521-0103
Topics:
Medicine
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