10.3389/fimmu.2018.00762.s003
Xiaozhi Bai
Xiaozhi
Bai
Ting He
Ting
He
Yang Liu
Yang
Liu
Julei Zhang
Julei
Zhang
Xiaoqiang Li
Xiaoqiang
Li
Jihong Shi
Jihong
Shi
Kejia Wang
Kejia
Wang
Fu Han
Fu
Han
Wei Zhang
Wei
Zhang
Yijie Zhang
Yijie
Zhang
Weixia Cai
Weixia
Cai
Dahai Hu
Dahai
Hu
Image_3_Acetylation-Dependent Regulation of Notch Signaling in Macrophages by SIRT1 Affects Sepsis Development.TIF
Frontiers
2018
sepsis
SIRT1
Notch
macrophage
deacetylate
2018-05-07 06:29:45
Figure
https://frontiersin.figshare.com/articles/figure/Image_3_Acetylation-Dependent_Regulation_of_Notch_Signaling_in_Macrophages_by_SIRT1_Affects_Sepsis_Development_TIF/6226493
<p>SIRT1 is reported to participate in macrophage differentiation and affect sepsis, and Notch signaling is widely reported to influence inflammation and macrophage activation. However, the specific mechanisms through which SIRT1 regulates sepsis and the relationship between SIRT1 and Notch signaling remain poorly elucidated. In this study, we found that SIRT1 levels were decreased in sepsis both in vitro and in vivo and that SIRT1 regulation of Notch signaling affected inflammation. In lipopolysaccharide (LPS)-induced sepsis, the levels of Notch signaling molecules, including Notch1, Notch2, Hes1, and intracellular domain of Notch (NICD), were increased. However, NICD could be deacetylated by SIRT1, and this led to the suppression of Notch signaling. Notably, in macrophages from myeloid-specific RBP-J<sup>−/−</sup> mice, in which Notch signaling is inhibited, pro-inflammatory cytokines were expressed at lower levels than in macrophages from wild-type littermates and in RBP-J<sup>−/−</sup> macrophages, and the NF-κB pathway was also inhibited. Accordingly, in the case of RBP-J<sup>−/−</sup> mice, LPS-induced inflammation and mortality were lower than in wild-type mice. Our results indicate that SIRT1 inhibits Notch signaling through NICD deacetylation and thus ultimately alleviates sepsis.</p>