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ID 48598
本文ファイル
著者
Ishihara, Yasuhiro 大学院総合科学研究科 広大研究者総覧
Itoh, Kouichi
Ishida, Atsuhiko 大学院総合科学研究科 広大研究者総覧
Yamazaki, Takeshi 大学院総合科学研究科 広大研究者総覧
抄録(英)
Microglia are activated quickly in response to external pathogens or cell debris and clear these substances via the inflammatory response. However, excessive activation of microglia can be harmful to host cells due to the increased production of reactive oxygen species and proinflammatory cytokines. Superoxide dismutase 2 (SOD2) is reportedly induced under various inflammatory conditions in the central nervous system. We herein demonstrated that activated microglia strongly express SOD2 and examined the role of SOD2, focusing on regulation of the microglial activity and the susceptibility of microglia to oxidative stress. When rat primary microglia were treated with LPS, poly(I:C), peptidoglycan, or CpG oligodeoxynucleotide, respectively, the mRNA and protein levels of SOD2 largely increased. However, an increased expression of SOD2 was not detected in the primary neurons or astrocytes, indicating that SOD2 is specifically induced in microglia under inflammatory conditions. The activated microglia showed high tolerance to oxidative stress, whereas SOD2 knockdown conferred vulnerability to oxidative stress. Interestingly, the production of proinflammatory cytokines was increased in the activated microglia treated with SOD2 siRNA compared with that observed in the control siRNA-treated cells. Pretreatment with NADPH oxidase inhibitors, diphenylene iodonium and apocynin, decreased in not only reactive oxygen species generation but also the proinflammatory cytokine expression. Notably, SOD2 knockdown largely potentiated the nuclear factor κB activity in the activated microglia. Taken together, increased SOD2 conferred tolerance to oxidative stress in the microglia and decreased proinflammatory cytokine production by attenuating the nuclear factor κB activity. Therefore, SOD2 might regulate neuroinflammation by controlling the microglial activities.
内容記述
This work was supported in part by KAKENHI Grants 26740024, 30291149, and 22310041 from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (to Y. I., K. I., and T. Y.); a grant from the Fujii Foundation (to Y. I.); and a grant from the Hiroshima University Education and Research Support Foundation (to Y. I.).
掲載誌名
Journal of Biological Chemistry
290巻
37号
開始ページ
22805
終了ページ
22817
出版年月日
2015-09-11
出版者
The American Society for Biochemistry and Molecular Biology, Inc.
ISSN
0021-9258
1083-351X
出版者DOI
言語
英語
NII資源タイプ
学術雑誌論文
広大資料タイプ
学術雑誌論文
DCMIタイプ
text
フォーマット
application/pdf
著者版フラグ
publisher
権利情報
This research was originally published in the Journal of Biological Chemistry. Yasuhiro Ishihara, Takuya Takemoto, Kouichi Itoh, Atsuhiko Ishida, and Takeshi Yamazaki. Dual Role of Superoxide Dismutase 2 Induced in Activated Microglia: OXIDATIVE STRESS TOLERANCE AND CONVERGENCE OF INFLAMMATORY RESPONSES. J. Biol. Chem. 2015; 290(37):22805-22817. © the American Society for Biochemistry and Molecular Biology.
関連情報URL
部局名
総合科学研究科