STAT3 mediates protection from liver inflammation after partial hepatectomy.
OBJECTIVE
The liver has the unique capacity to restore its mass by hepatocyte proliferation after injury or transplantation. The present study investigated whether the regenerating liver responds to immune stimuli in the same way as the quiescent one.


METHODS
We performed partial hepatectomy (PHx) in mice, then stimulated the mice with concanavalin A (ConA) to study their immune responses. Plasma Alanine aminotransferase (ALT) and cytokine levels as well as liver inflammatory infiltration were measured to evaluate liver damage. Transcriptional factors were further detected to study the underlining mechanisms.


RESULTS
Our results showed that PHx mice were resistant to ConA-induced liver inflammation and injury, as evidenced by both morphological and biochemical observations. Then we went further to study the mechanisms. We found marked signal transducer and activator of transcription 3 (STAT3) activation 48 hours after PHx. When STAT3 activation was blocked with its inhibitor JSI-124, PHx mice also developed severe liver inflammation after ConA stimulation.


CONCLUSIONS
The regenerating liver is resistant to ConA induced immune assaulting, and STAT3 is the major player in the protection process.
Xu
Yan
Y
Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences/Shanghai Jiaotong University School of Medicine, Shanghai, China.
Feng
Dechun
D
Wang
Ying
Y
Luo
Qingqiong
Q
Xu
Lingyun
L
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D003208:Concanavalin A / Q000494:pharmacology; D016207:Cytokines / Q000097:blood; D015536:Down-Regulation; D006498:Hepatectomy; D006505:Hepatitis / Q000276:immunology / Q000378:metabolism*; D008099:Liver / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008115:Liver Regeneration / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D013997:Time Factors
D016207:Cytokines; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D003208:Concanavalin A; D000410:Alanine Transaminase