このエントリーをはてなブックマークに追加
ID 51464
フルテキストURL
著者
Wakabayashi, Hiroshi Okayama Univ, Dept Pathol & Expt Med, Grad Sch Med Dent & Pharmaceut Sci
Ito, Toshihiro Okayama Univ, Dept Pathol & Expt Med, Grad Sch Med Dent & Pharmaceut Sci
Fushimi, Soichiro Okayama Univ, Dept Pathol & Expt Med, Grad Sch Med Dent & Pharmaceut Sci
Nakashima, Yuki Okayama Univ, Dept Pathol & Expt Med, Grad Sch Med Dent & Pharmaceut Sci
Itakura, Jyunya Okayama Univ, Dept Pathol & Expt Med, Grad Sch Med Dent & Pharmaceut Sci
Liu, Qiuying Okayama Univ, Dept Pathol & Expt Med, Grad Sch Med Dent & Pharmaceut Sci
Win, Min Min Okayama Univ, Dept Pathol & Expt Med, Grad Sch Med Dent & Pharmaceut Sci
Sun, Cuiming Okayama Univ, Dept Pathol & Expt Med, Grad Sch Med Dent & Pharmaceut Sci
Chen, Cao Okayama Univ, Dept Pathol & Expt Med, Grad Sch Med Dent & Pharmaceut Sci
Sato, Miwa Okayama Univ, Dept Pathol & Expt Med, Grad Sch Med Dent & Pharmaceut Sci
Mino, Megumi Okayama Univ, Dept Pathol & Expt Med, Grad Sch Med Dent & Pharmaceut Sci
Ogino, Tetsuya Okayama Univ, Dept Pathol & Expt Med, Grad Sch Med Dent & Pharmaceut Sci
Makino, Hirofumi Okayama Univ, Dept Med & Clin Sci, Grad Sch Med Dent & Pharmaceut Sci
Yoshimura, Akihiko Keio Univ, Sch Med, Dept Microbiol & Immunol
Matsukawa, Akihiro Okayama Univ, Dept Pathol & Expt Med, Grad Sch Med Dent & Pharmaceut Sci
抄録
MAPKs are involved in acetaminophen (APAP)-hepatotoxicity, but the regulatory mechanism remains unknown. Here, we explored the role of Spred-2 that negatively regulates Ras/ERK pathway in APAP-hepatotoxicity. Spred-2 knockout (KO) mice demonstrated exacerbated liver injury, an event that was associated with increased numbers of CD4(+) T, CD8(+) T and NK cells in the liver compared to the control. Levels of CXCL9/CXCL10 that attract and activate these cells were increased in Spred-2 KO-liver. Kupffer cells isolated from Spred-2 KO mice after APAP challenge expressed higher levels of CXCL9/CXCL10 than those from the control. Upon stimulation with APAP or IFN gamma, naive Kupffer cells from Spred-2 KO mice expressed higher levels of CXCL9/CXCL10. NK cell-depletion attenuated APAP-hepatotoxicity with lowered hepatic IFN gamma and decreased numbers of not only NK cells but also CD4(+) T and CD8(+) T cells in the liver. These results suggest that Spred-2 negatively regulates APAP-hepatotoxicity under the control of Kupffer cells and NK cells.
キーワード
Acetaminophen
Hepatotoxicity
Liver immunology
Signaling pathway
Toxicology
発行日
2012-09
出版物タイトル
Clinical Immunology
144巻
3号
出版者
Academic Press Inc Elsevier Science
開始ページ
272
終了ページ
282
ISSN
1521-6616
資料タイプ
学術雑誌論文
オフィシャル URL
http://dx.doi.org/10.1016/j.clim.2012.07.002
関連URL
http://ousar.lib.okayama-u.ac.jp/metadata/51459
言語
English
OAI-PMH Set
岡山大学
著作権者
(C) 2012 Elsevier Inc. All rights reserved.
論文のバージョン
author
査読
有り
DOI
Web of Sience KeyUT