| First Author | Yin S | Year | 2011 |
| Journal | Am J Pathol | Volume | 178 |
| Issue | 4 | Pages | 1614-21 |
| PubMed ID | 21435447 | Mgi Jnum | J:169853 |
| Mgi Id | MGI:4943356 | Doi | 10.1016/j.ajpath.2011.01.001 |
| Citation | Yin S, et al. (2011) Enhanced Liver Regeneration in IL-10-Deficient Mice after Partial Hepatectomy via Stimulating Inflammatory Response and Activating Hepatocyte STAT3. Am J Pathol 178(4):1614-21 |
| abstractText | Emerging evidence suggests that proinflammatory cytokines, including tumor necrosis factor-alpha (TNF-alpha) 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-alpha, and IFN-gamma) 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. |
