Jia Yanhui, Han Shichao, Li Jun, Wang Hongtao, Liu Jiaqi, Li Na, Yang Xuekang, Shi Jihong, Han Juntao, Li Yan, Bai Xiaozhi, Su Linlin, Hu Dahai
Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
Innate Immun. 2017 Feb;23(2):188-195. doi: 10.1177/1753425916683751. Epub 2016 Dec 23.
The type III histone deacetylase SIRT1 has recently emerged as a critical immune regulator by suppressing T-cell immunity and macrophage activation during inflammation, but its mechanism in regulating inflammatory response in macrophages remains unclear. Here we show that the expression of SIRT1 in macrophage cells decreased following the release of inflammation cytokines when the cells were stimulated with LPS. IRF8, an important regulator in monocyte differentiation and macrophage polarization, showed the opposite trend, with SIRT1 expression levels increasing after the cells treated with LPS. Co-immunoprecipitation and immunofluorescence experiments showed that SIRT1 could not only interact with IRF8, but also deacetylate it. LPS treatment had no effect on the expression of IRF8 in macrophage cells in which sirt1 was specifically deleted. Our results show that IRF8 may be the target of histone deacetylase SIRT1 to regulate the inflammation in the macrophage cells.
III型组蛋白去乙酰化酶SIRT1最近已成为一种关键的免疫调节因子，它通过在炎症期间抑制T细胞免疫和巨噬细胞活化来发挥作用，但其在调节巨噬细胞炎症反应中的机制仍不清楚。在这里，我们表明，当用脂多糖（LPS）刺激巨噬细胞时，炎症细胞因子释放后，SIRT1在巨噬细胞中的表达会降低。IRF8是单核细胞分化和巨噬细胞极化中的重要调节因子，呈现相反的趋势，在用LPS处理细胞后，SIRT1表达水平增加。免疫共沉淀和免疫荧光实验表明，SIRT1不仅可以与IRF8相互作用，还可以使其去乙酰化。在sirt1被特异性敲除的巨噬细胞中，LPS处理对IRF8的表达没有影响。我们的结果表明，IRF8可能是组蛋白去乙酰化酶SIRT1调节巨噬细胞炎症的靶点。
