期刊
JOURNAL OF CLINICAL INVESTIGATION
卷 131, 期 1, 页码 -出版社
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI130740
关键词
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资金
- Summit Program, Academia Sinica [AS-SUMMIT-109]
- Ministry of Science and Technology [MOST 104-0210-01-09-02, MOST 105-0210-01-13-01, MOST 106-0210-01-15-02, AS-KPQ-109-BioMed, MOST 109-0210-01-18-02]
- Academia Sinica Core Facility and Innovative Instrument Project [AS-CFII-108-107]
The study found that the expression of galectin-7 is reduced in skin lesions of psoriasis patients, and IL-17A and TNF-alpha suppress galectin-7 expression in human keratinocytes. Galectin-7 attenuates the production of inflammatory mediators by keratinocytes via the microRNA-146a/ERK pathway when cells are stimulated with IL-17A. Fluvastatin was identified as an inducer of galectin-7 expression and showed potential in reducing IL-6 and IL-8 production induced by IL-17A.
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-alpha, 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.
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