| Autor: |
Chen HL; Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan., Lo CH; Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan., Huang CC; Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan., Lu MP; Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan., Hu PY; Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan., Chen CS; Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan., Chueh DY; Research Center for Applied Sciences, Academia Sinica, Taipei, Taiwan., Chen P; Research Center for Applied Sciences, Academia Sinica, Taipei, Taiwan., Lin TN; Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan., Lo YH; Department of Dermatology, Fu Jen Catholic University Hospital, and.; School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan., Hsiao YP; Chung Shan Medical University Hospital, Taichung, Taiwan., Hsu DK; Department of Dermatology, School of Medicine, University of California, Davis, Sacramento, California, USA., Liu FT; Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.; Department of Dermatology, School of Medicine, University of California, Davis, Sacramento, California, USA. |
| Abstrakt: |
Psoriasis is a chronic inflammatory skin disease characterized by inflammatory cell infiltration, as well as hyperproliferation of keratinocytes in skin lesions, and is considered a metabolic syndrome. We found that the expression of galectin-7 is reduced in skin lesions of patients with psoriasis. IL-17A and TNF-α, 2 cytokines intimately involved in the development of psoriatic lesions, suppressed galectin-7 expression in human primary keratinocytes (HEKn cells) and the immortalized human keratinocyte cell line HaCaT. A galectin-7 knockdown in these cells elevated the production of IL-6 and IL-8 and enhanced ERK signaling when the cells were stimulated with IL-17A. Galectin-7 attenuated IL-17A-induced production of inflammatory mediators by keratinocytes via the microRNA-146a/ERK pathway. Moreover, galectin-7-deficient mice showed enhanced epidermal hyperplasia and skin inflammation in response to intradermal IL-23 injection. We identified fluvastatin as an inducer of galectin-7 expression by connectivity map analysis, confirmed this effect in keratinocytes, and demonstrated that fluvastatin attenuated IL-6 and IL-8 production induced by IL-17A. Thus, we validate a role of galectin-7 in the pathogenesis of psoriasis, in both epidermal hyperplasia and keratinocyte-mediated inflammatory responses, and formulate a rationale for the use of statins in the treatment of psoriasis. |
