Glycogen synthase kinase-3 (GSK-3) facilitates interferon (IFN)-γ signaling. Because IFN-γ 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-γ-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-γ receptor 1-mediated deregulation of intercellular adhesion molecule 1 (CD54). TPA/IFN-γ 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-γ production and the nuclear translocation of T-box transcription factor Tbx21, a transcription factor of IFN-γ, 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-γ signaling but also to regulate IFN-γ production. Inhibiting GSK-3 may be a potential treatment strategy for preventing such effects.
|頁（從 - 到）||125-133|
|期刊||Journal of Pharmacology and Experimental Therapeutics|
|出版狀態||已發佈 - 十月 2012|
ASJC Scopus subject areas
- Molecular Medicine
Hsieh, C-Y., Chen, C-L., Tsai, C-C., Huang, W-C., Tseng, P-C., Lin, Y-S., Chen, S-H., Wong, T-W., Choi, P-C., & Lin, C. F. (2012). Inhibiting glycogen synthase kinase-3 decreases 12-O-tetradecanoylphorbol- 13-acetate-induced interferon-γ-mediated skin inflammation. Journal of Pharmacology and Experimental Therapeutics, 343(1), 125-133. https://doi.org/10.1124/jpet.112.194100