Cilostazol Suppresses IL-23 Production in Human Dendritic Cells via an AMPK-Dependent Pathway

作者：Quanxing Shi, Zhao Yin, Peilin Liu, Bei Zhao, Zhong Zhang, Shuai Mao, Tengfei Wei, Mengmeng Rao, Liguo Zhang, Shouli Wang · 发表于：Cellular Physiology and Biochemistry · 年份：2016 · DOI：10.1159/000452564 · 被引用次数：10 · 研究领域：Psoriasis: Treatment and Pathogenesis、Cytokine Signaling Pathways and Interactions、Dermatology and Skin Diseases

BACKGROUND/AIMS: Cilostazol has been previously demonstrated to inhibit IL-23 production in human synovial macrophages via a RhoA/ROCK-dependent pathway. However, whether cilostazol affects IL-23 production in human dendritic cells remains largely unknown. The present study was designed to investigate this question and elucidate the possible underlying mechanisms. METHODS: Human monocyte-derived dendritic cells (mo-DCs) were pretreated with or without cilostazol and then incubated with zymosan. Enzyme-linked immunosorbent assay (ELISA) and real time PCR analyses were used to measure IL-23 protein expression and RNA levels, respectively, whereas Western blotting was used to measure the expression and phosphorylation level of AMPK. RESULTS: Our results demonstrated that cilostazol suppressed zymosan-induced IL-23 protein production in a concentration dependent manner without affecting dendritic cell viability. In addition, it was found that cilostazol suppressed the expression of the p19 and p40 subunits of IL-23. Moreover, cilostazol mimicked the effect of the AMPK agonist A-769662, as demonstrated by the fact that IL-23 production was also inhibited by A-769662, and the effect of cilostazol on IL-23 production was blocked by the AMPK antagonist Compound C. More importantly, Western blotting demonstrated that cilostazol led to an increased phosphorylation of AMPK. CONCLUSION: Collectively, our data suggest that cilostazol inhibits the production of IL-23 in human mo-DCs, poten...