title: Interleukin-22 ameliorates liver fibrogenesis by attenuating hepatic stellate cell activation and downregulating the levels of inflammatory cytokines.
abstract: OBJECTIVE
  To investigate the effect of interleukin (IL)-22 on hepatic fibrosis in mice and the possible mechanism involved.
  
  
  METHODS
  Liver fibrosis was induced in male BALB/c mice by CCl₄. Recombinant IL-22 (rmIL-22) was administered intraperitoneally in CCl₄-treated mice. Fibrosis was assessed by histology and Masson staining. The activation of hepatic stellate cells (HSCs) was investigated by analysis of α-smooth muscle actin expression. The frequencies of T helper (Th) 22 cells, Th17 cells and Th1 cells, the expression of inflammatory cytokines [IL-22, IL-17A, interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), IL-6, IL-1β] and transcription factors [aryl hydrocarbon receptor (AHR), RAR-related orphan receptor (RORγt), T-bet] mRNA in the liver were investigated. In addition, the plasma levels of IL-22, IL-17A, IFN-γ, TNF-α, IL-6 and IL-1β were evaluated.
  
  
  RESULTS
  Significant elevations in circulating Th22 cells, Th17 cells, Th1 cells, IL-22, IL-17A, and IFN-γ were observed in the hepatic fibrosis group compared with the control group (P < 0.01). Treatment with rmIL-22 in mice with hepatic fibrosis ameliorated the severity of hepatic fibrosis, which was confirmed by lower hepatic fibrosis pathological scores (P < 0.01). RmIL-22 decreased the frequencies of Th22 cells (6.71% ± 0.97% vs 8.09% ± 0.74%, P < 0.01), Th17 cells (4.34% ± 0.37% vs 5.71% ± 0.24%, P < 0.01), Th1 cells (3.09% ± 0.49% vs 4.91% ± 0.73%, P < 0.01), and the levels of IL-22 (56.23 ± 3.08 vs 70.29 ± 3.01, P < 0.01), IL-17A (30.74 ± 2.77 vs 45.68 ± 2.71, P < 0.01), and IFN-γ (74.78 ± 2.61 vs 124.89 ± 2.82, P < 0.01). Down-regulation of IL-22, IL-17A, IFN-γ, TNF-α, IL-6, IL-1β, AHR RORγt, and T-bet gene expression in the liver was observed in the rmIL-22 group (P < 0.01).
  
  
  CONCLUSIONS
  The frequencies of Th22, Th17 and Th1 cells are elevated in hepatic fibrosis. RmIL-22 can attenuate HSC activation and down-regulate the levels of inflammatory cytokines, thereby ameliorating liver fibrogenesis.
authors: Dong-Hong Lu, Xiao-Yun Guo, Shan-Yu Qin, Wei Luo, Xiao-Li Huang, Mei Chen, Jia-Xu Wang, Shi-Jia Ma, Xian-Wen Yang, Hai-Xing Jiang, Department of Gastroenterology, The First Affiliated Hospital, Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China.
authors: Dong-Hong
authors: DH
authors: Lu
authors: Dong-Hong Lu, Xiao-Yun Guo, Shan-Yu Qin, Wei Luo, Xiao-Li Huang, Mei Chen, Jia-Xu Wang, Shi-Jia Ma, Xian-Wen Yang, Hai-Xing Jiang, Department of Gastroenterology, The First Affiliated Hospital, Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China.
authors: Xiao-Yun
authors: XY
authors: Guo
authors: Dong-Hong Lu, Xiao-Yun Guo, Shan-Yu Qin, Wei Luo, Xiao-Li Huang, Mei Chen, Jia-Xu Wang, Shi-Jia Ma, Xian-Wen Yang, Hai-Xing Jiang, Department of Gastroenterology, The First Affiliated Hospital, Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China.
authors: Shan-Yu
authors: SY
authors: Qin
authors: Dong-Hong Lu, Xiao-Yun Guo, Shan-Yu Qin, Wei Luo, Xiao-Li Huang, Mei Chen, Jia-Xu Wang, Shi-Jia Ma, Xian-Wen Yang, Hai-Xing Jiang, Department of Gastroenterology, The First Affiliated Hospital, Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China.
authors: Wei
authors: W
authors: Luo
authors: Dong-Hong Lu, Xiao-Yun Guo, Shan-Yu Qin, Wei Luo, Xiao-Li Huang, Mei Chen, Jia-Xu Wang, Shi-Jia Ma, Xian-Wen Yang, Hai-Xing Jiang, Department of Gastroenterology, The First Affiliated Hospital, Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China.
authors: Xiao-Li
authors: XL
authors: Huang
authors: Dong-Hong Lu, Xiao-Yun Guo, Shan-Yu Qin, Wei Luo, Xiao-Li Huang, Mei Chen, Jia-Xu Wang, Shi-Jia Ma, Xian-Wen Yang, Hai-Xing Jiang, Department of Gastroenterology, The First Affiliated Hospital, Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China.
authors: Mei
authors: M
authors: Chen
authors: Dong-Hong Lu, Xiao-Yun Guo, Shan-Yu Qin, Wei Luo, Xiao-Li Huang, Mei Chen, Jia-Xu Wang, Shi-Jia Ma, Xian-Wen Yang, Hai-Xing Jiang, Department of Gastroenterology, The First Affiliated Hospital, Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China.
authors: Jia-Xu
authors: JX
authors: Wang
authors: Dong-Hong Lu, Xiao-Yun Guo, Shan-Yu Qin, Wei Luo, Xiao-Li Huang, Mei Chen, Jia-Xu Wang, Shi-Jia Ma, Xian-Wen Yang, Hai-Xing Jiang, Department of Gastroenterology, The First Affiliated Hospital, Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China.
authors: Shi-Jia
authors: SJ
authors: Ma
authors: Dong-Hong Lu, Xiao-Yun Guo, Shan-Yu Qin, Wei Luo, Xiao-Li Huang, Mei Chen, Jia-Xu Wang, Shi-Jia Ma, Xian-Wen Yang, Hai-Xing Jiang, Department of Gastroenterology, The First Affiliated Hospital, Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China.
authors: Xian-Wen
authors: XW
authors: Yang
authors: Dong-Hong Lu, Xiao-Yun Guo, Shan-Yu Qin, Wei Luo, Xiao-Li Huang, Mei Chen, Jia-Xu Wang, Shi-Jia Ma, Xian-Wen Yang, Hai-Xing Jiang, Department of Gastroenterology, The First Affiliated Hospital, Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China.
authors: Hai-Xing
authors: HX
authors: Jiang
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002251:Carbon Tetrachloride; D016207:Cytokines / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D055166:Hepatic Stellate Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism*; D007378:Interleukins / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D012720:Severity of Illness Index; D015398:Signal Transduction / Q000187:drug effects; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D058504:Th17 Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D013997:Time Factors; D000097043:Interleukin-22
chemical_list: D000893:Anti-Inflammatory Agents; D002251:Carbon Tetrachloride; D016207:Cytokines; D018836:Inflammation Mediators; D007378:Interleukins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D000097043:Interleukin-22
keywords: Hepatic fibrosis; Interleukin-22; T helper 1 cells; T helper 17 cells; T helper 22 cells