HMGB1 silencing in macrophages prevented their functional skewing and ameliorated EAM development: Nuclear HMGB1 may be a checkpoint molecule of macrophage reprogramming
HMGB1 silencing in macrophages prevented their functional skewing and ameliorated EAM development: Nuclear HMGB1 may be a checkpoint molecule of macrophage reprogramming
复制标题
巨噬细胞中的 HMGB1 沉默可防止其功能偏差并改善 EAM 发育：核 HMGB1 可能是巨噬细胞重编程的检查点分子
DOI：
10.1016/j.intimp.2018.01.013
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发表时间：
2018-03-01
影响因子：
5.6
通讯作者：
Su, Zhaoliang
中科院分区：
文献类型：
--
作者：
Jiang, Yuanyuan;Chen, Rong;Su, Zhaoliang
High-mobility group box 1 (HMGB1), an important inflammatory factor, plays significant roles in CD4(+) T cell differentiation, cancer and autoimmune disease development. Our previous data have demonstrated that HMGB1 contributes to macrophage reprogramming and is involved in experimental autoimmune myocarditis (EAM) development. In contrast to the well-explored function of HMGB1, little is known about the nuclear function. Whether HMGB1 can serve as an architectural factor and control functional skewing of macrophages remains unclear. Therefore, the present work was performed to address the above speculation. The adenovirus-mediated shRNA (Ad-shRNA) was employed to knock down HMGB1 in RAW264.7 and monocytes/macrophages of EAM mice. Our data showed that in vitro HMGB1 silencing limited functional skewing of macrophages and down-regulated inflammatory factors secretion, which can't be reversed by the exogenous HMGB1. In Ml polarization system, the phosphorylations of NF-kappa B, p38 and Erk1/2 were inhibited following HMGB1 silencing. In vivo, HMGB1 silencing could effectively ameliorate EAM development. Our data suggest that HMGB1 may be a checkpoint nuclear factor of macrophage reprogramming. Our findings also provide an exciting therapeutic method for inflammatory disorders.
