title: SIRT2 Plays Significant Roles in Lipopolysaccharides-Induced Neuroinflammation and Brain Injury in Mice.
abstract: Several recent studies have suggested seemingly contrasting roles of SIRT2 in inflammation: Our previous cell culture study has indicated that SIRT2 siRNA-produced decrease in SIRT2 levels can lead to significant inhibition of lipopolysaccharides (LPS)-induced activation of BV2 microglia, suggesting that SIRT2 is required for LPS-induced microglial activation. In contrast, some studies have suggested that SIRT2 deficiency can lead to increased inflammation. In our current study, we used a mouse model of neuroinflammation to determine the roles of SIRT2 in LPS-induced inflammation. We found that administration of SIRT2 inhibitor AGK2 can significantly decrease LPS-induced increases in CD11b signals and the mRNA of TNF-α and IL-6. We further found that AGK2 can block LPS-induced nuclear translocation of NFκB. In addition, our study has shown that AGK2 can decrease not only LPS-induced increase in TUNEL signals-a marker of apoptosis-like damage, but also LPS-induced increases in the levels of active Caspase-3 and Bax. Collectively, our current in vivo study, together with our previous cell culture study, has suggested that SIRT2 is required for LPS-induced neuroinflammation and brain injury.
authors.affiliation: Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai, 200030, People's Republic of China.
authors.forename: Ban
authors.initials: B
authors.lastname: Wang
authors.affiliation: Cardiology Department, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, 200030, People's Republic of China.
authors.forename: Youjun
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai, 200030, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Cao
authors.affiliation: Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai, 200030, People's Republic of China.
authors.forename: Xunbing
authors.initials: X
authors.lastname: Wei
authors.affiliation: Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: James
authors.initials: J
authors.lastname: Chen
authors.affiliation: Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai, 200030, People's Republic of China. weihaiy@sjtu.edu.cn.|Department of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201999, People's Republic of China. weihaiy@sjtu.edu.cn.
authors.forename: Weihai
authors.initials: W
authors.lastname: Ying
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001930:Brain Injuries / Q000188:drug therapy / Q000378:metabolism*; D004195:Disease Models, Animal; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism*; D056565:Sirtuin 2 / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; C418743:Sirt2 protein, mouse; D056565:Sirtuin 2
keywords: Apoptosis; Brain; Cytokines; Neuroinflammation; SIRT2