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
publons
Ito, Toshihiro
Okayama Univ, Dept Pathol & Expt Med, Grad Sch Med Dent & Pharmaceut Sci
ORCID
Kaken ID
publons
researchmap
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
ORCID
Kaken ID
publons
researchmap
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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.
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キーワード | Acetaminophen
Hepatotoxicity
Liver immunology
Signaling pathway
Toxicology
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発行日 | 2012-09
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出版物タイトル |
Clinical Immunology
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巻 | 144巻
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号 | 3号
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出版者 | Academic Press Inc Elsevier Science
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開始ページ | 272
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終了ページ | 282
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ISSN | 1521-6616
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資料タイプ |
学術雑誌論文
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オフィシャル URL | http://dx.doi.org/10.1016/j.clim.2012.07.002
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関連URL | http://ousar.lib.okayama-u.ac.jp/metadata/51459
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言語 |
英語
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著作権者 | (C) 2012 Elsevier Inc. All rights reserved.
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論文のバージョン | author
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査読 |
有り
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DOI | |
Web of Science KeyUT |