title: Enhanced liver regeneration in IL-10-deficient mice after partial hepatectomy via stimulating inflammatory response and activating hepatocyte STAT3.
abstract: Emerging evidence suggests that proinflammatory cytokines, including tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), play a critical role in the initiation and progression of liver regeneration; however, relatively little is known about the role of anti-inflammatory cytokine IL-10 in liver regeneration after partial hepatectomy (PHx). Here, we examined the role of IL-10 in liver regeneration using a model of PHx in several strains of genetically modified mice. After PHx, expression of IL-10 mRNA in the liver and spleen was significantly elevated. Such elevation was diminished in TLR4 mutant mice. Compared with wild-type mice, IL-10(-/-) mice had higher levels of expression of proinflammatory cytokines (IL-6, TNF-α, and IFN-γ) and inflammatory markers (CCR2 and F4/80) in the liver, as well as higher serum levels of proinflammatory cytokines after PHx. The number of neutrophils and macrophages was also higher in the livers of IL-10(-/-) mice than in wild-type mice after PHx. Liver regeneration as determined by BrdU incorporation after PHx was higher in IL-10(-/-) mice than in wild-type mice, which was associated with higher levels of activation of IL-6 downstream signal STAT3 in the liver. An additional deletion of STAT3 in hepatocytes significantly reduced liver regeneration in IL-10(-/-) mice after PHx. Collectively, IL-10 plays an important role in negatively regulating liver regeneration via limiting inflammatory response and subsequently tempering hepatic STAT3 activation.
authors: Institute of Clinical Pharmacology, Ministry of Education, Anhui Medical University, Anhui, China.
authors: Shi
authors: S
authors: Yin
authors: Hua
authors: H
authors: Wang
authors: Ogyi
authors: O
authors: Park
authors: Wei
authors: W
authors: Wei
authors: Jilong
authors: J
authors: Shen
authors: Bin
authors: B
authors: Gao
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism; D005786:Gene Expression Regulation; D006498:Hepatectomy / Q000379:methods; D022781:Hepatocytes / Q000166:cytology; D007249:Inflammation; D016753:Interleukin-10 / Q000235:genetics* / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008115:Liver Regeneration; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D013154:Spleen / Q000378:metabolism
chemical_list: D016207:Cytokines; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D016753:Interleukin-10