机构：[a]Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases and Institute of Neuroscience, Soochow University, Suzhou, Jiangsu 215021, China[b]Department of Neurology, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China[c]Department of Pharmacology, School of Pharmaceutical Science, Soochow University, Suzhou 215123, China[d]Cytoneurobiology Unit & Department of Anatomy, Medical College of Soochow University, Suzhou 215123, China
Microglia-mediated neuroinflammation is implicated in the pathogenesis of several neurodegenerative disorders. Microglia can be activated and polarized to exert pro- or anti-inflammatory roles in response to specific stimulus. Rotenone is an environmental toxin that has been shown to activate microglia and neuroinflammation. However, the effects and mechanisms of rotenone on microglia polarization are poorly studied. In the present study, we demonstrated that rotenone enhanced the levels of M1 phenotypic genes including TNF-alpha, iNOS and COX-2/PGE(2) but reduced that of M2 markers such as Ym1/2 and IL-10 in mouse primary and immortalized microglia. Moreover, the transcription and protein expression of cystathionine-beta-synthase (CBS), as well as hydrogen sulfide (H2S) production were decreased in rotenone-treated primary microglia. Elevating endogenous H2S via CBS over-expression in immortalized microglia not only reduced the expression of pro-inflammatory M1 genes, but also enhanced the anti-inflammatory M2 marker IL-10 production in response to rotenone stimulation as compared to vector-transfected cells. Similarly, pretreatment with H2S donor NaHS (50, 100 and 500 mu mol/L) attenuated the increases of M1 gene expression triggered by rotenone treatment, and enhanced the M2 gene Ym1/2 expression in mouse primary microglia. In addition, we observed reactive oxygen species (ROS) scavenger N-acetyl-L-cysteine reversed the down-regulation of CBS and H2S generation caused by rotenone in microglia. NaHS pretreatment also decreased the ROS formation in rotenone-stimulated microglia. Taken together, these results reveal that probably via triggering ROS formation, rotenone suppressed the CBS-H2S pathway and thus promoted microglia polarization toward M1 pro-inflammatory phenotype. (C) 2014 Elsevier Inc. All rights reserved.
基金：
Grants from the National Natural
Science Foundation of China (81171212, 81371278), Natural Science
Foundation of Jiangsu Province (BK2010228 and
BK2011294) and Natural Science Foundation of Higher Education
Institutions of Jiangsu Province (11KJB310010).
第一作者机构：[a]Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases and Institute of Neuroscience, Soochow University, Suzhou, Jiangsu 215021, China[c]Department of Pharmacology, School of Pharmaceutical Science, Soochow University, Suzhou 215123, China
共同第一作者：
通讯作者：
通讯机构：[*]Institute of Neuroscience, Soochow University, 199 Ren-Ai Road, Suzhou Industrial Park, Suzhou 215123, China.
推荐引用方式(GB/T 7714)：
Chenchen Du,Mengmeng Jin,Yu Hong,et al.Downregulation of cystathionine beta-synthase/hydrogen sulfide contributes to rotenone-induced microglia polarization toward M1 type[J].BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS.2014,451(2):239-45.doi:10.1016/j.bbrc.2014.07.107.
APA：
Chenchen Du,Mengmeng Jin,Yu Hong,Qian Li,Xian-Hui Wang...&Li-Fang Hu.(2014).Downregulation of cystathionine beta-synthase/hydrogen sulfide contributes to rotenone-induced microglia polarization toward M1 type.BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,451,(2)
MLA：
Chenchen Du,et al."Downregulation of cystathionine beta-synthase/hydrogen sulfide contributes to rotenone-induced microglia polarization toward M1 type".BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 451..2(2014):239-45
