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Interleukin-11 links oxidative stress and compensatory proliferation.
MedLine Citation:
PMID:  22253262     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Apoptotic cells can stimulate the compensatory proliferation of surrounding cells to maintain tissue homeostasis. Although oxidative stress is associated with apoptosis and necrosis, whether it contributes to compensatory proliferation is unknown. Here, we showed that interleukin-11 (IL-11), a member of the IL-6 family of proinflammatory cytokines, was produced by cells in an oxidative stress-dependent manner. IL-11 production depended on the activation in dying cells of extracellular signal-regulated kinase 2, which in turn caused the phosphorylation and accumulation of the transcription factor Fra-1 by preventing its proteasome-dependent degradation. Fra-1 was subsequently recruited to the Il11 promoter and activated gene transcription. Upon acute liver injury in mice, IL-11 was mainly produced by hepatocytes in response to reactive oxygen species that were presumably released from dying hepatocytes. IL-11 that was secreted by the dying cells then induced the phosphorylation of the transcription factor STAT3 in adjacent healthy hepatocytes, which resulted in their compensatory proliferation. Furthermore, an IL-11 receptor (IL-11R) agonist enhanced the proliferation of hepatocytes and ameliorated oxidative stress upon acetaminophen-induced liver injury. Conversely, the effects of acetaminophen were exacerbated in mice deficient in the IL-11R α subunit. Together, these results suggest that IL-11 provides a functional link between oxidative stress and compensatory proliferation.
Authors:
Takashi Nishina; Sachiko Komazawa-Sakon; Saeko Yanaka; Xuehua Piao; Dong-Mei Zheng; Jiang-Hu Piao; Yuko Kojima; Shunhei Yamashina; Emiko Sano; Tracy Putoczki; Takahiro Doi; Takashi Ueno; Junji Ezaki; Hiroko Ushio; Matthias Ernst; Kouhei Tsumoto; Ko Okumura; Hiroyasu Nakano
Publication Detail:
Type:  Journal Article     Date:  2012-01-17
Journal Detail:
Title:  Science signaling     Volume:  5     ISSN:  1937-9145     ISO Abbreviation:  Sci Signal     Publication Date:  2012  
Date Detail:
Created Date:  2012-01-18     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101465400     Medline TA:  Sci Signal     Country:  United States    
Other Details:
Languages:  eng     Pagination:  ra5     Citation Subset:  IM    
Affiliation:
1Department of Immunology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
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