Interleukin-22 ameliorates liver fibrogenesis by attenuating hepatic stellate cell activation and downregulating the levels of inflammatory cytokines

AIM:To investigate the effect of interleukin(IL)-22 onhepatic fibrosis in mice and the possible mechanism involved.METHODS:Liver fibrosis was induced in male BALB/c mice by CCl4.Recombinant IL-22(rm IL-22) was administered intraperitoneally in CCl4-treated mice.Fibrosis was assessed by histology and...

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Published in:World journal of gastroenterology : WJG 2015-02, Vol.21 (5), p.1531-1545
Main Authors: Lu, Dong-Hong, Guo, Xiao-Yun, Qin, Shan-Yu, Luo, Wei, Huang, Xiao-Li, Chen, Mei, Wang, Jia-Xu, Ma, Shi-Jia, Yang, Xian-Wen, Jiang, Hai-Xing
Format: Article
Language:English
Subjects:
Animals
Anti-Inflammatory Agents - pharmacology
Basic Study
Carbon Tetrachloride
cel
cells
T
Cytokines - genetics
Cytokines - immunology
Cytokines - metabolism
helper
Hepatic Stellate Cells - drug effects
Hepatic Stellate Cells - immunology
Hepatic Stellate Cells - metabolism
Hepatic Stellate Cells - pathology
Inflammation Mediators - immunology
Inflammation Mediators - metabolism
Interleukin-22
Interleukins - pharmacology
Liver - drug effects
Liver - immunology
Liver - metabolism
Liver - pathology
Liver Cirrhosis, Experimental - chemically induced
Liver Cirrhosis, Experimental - genetics
Liver Cirrhosis, Experimental - immunology
Liver Cirrhosis, Experimental - metabolism
Liver Cirrhosis, Experimental - pathology
Liver Cirrhosis, Experimental - prevention & control
Male
Mice, Inbred BALB C
Recombinant Proteins - pharmacology
RNA, Messenger - metabolism
Severity of Illness Index
Signal Transduction - drug effects
Th1 Cells - drug effects
Th1 Cells - immunology
Th1 Cells - metabolism
Th17 Cells - drug effects
Th17 Cells - immunology
Th17 Cells - metabolism
Time Factors
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Summary:AIM:To investigate the effect of interleukin(IL)-22 onhepatic fibrosis in mice and the possible mechanism involved.METHODS:Liver fibrosis was induced in male BALB/c mice by CCl4.Recombinant IL-22(rm IL-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-17 A,interferon-γ(IFN-γ),tumor necrosis factor-α(TNF-α),IL-6,IL-1b] and transcription factors [aryl hydrocarbon receptor(AHR),RAR-related orphan receptor(RORγt),T-bet] m RNA in the liver were investigated.In addition,the plasma levels of IL-22,IL-17 A,IFN-γ,TNF-α,IL-6 and IL-1b were evaluated.RESULTS:Significant elevations in circulating Th22 cells,Th17 cells,Th1 cells,IL-22,IL-17 A,and IFN-γ were observed in the hepatic fibrosis group compared with the control group(P < 0.01).Treatment with rm IL-22 in mice with hepatic fibrosis ameliorated the severity of hepatic fibrosis,which was confirmed by lower hepatic fibrosis pathological scores(P < 0.01).Rm IL-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-17 A,IFN-γ,TNF-α,IL-6,IL-1b,AHR RORγt,and T-bet gene expression in the liver was observed in the rm IL-22 group(P < 0.01).CONCLUSION:The frequencies of Th22,Th17 andTh1 cells are elevated in hepatic fibrosis.Rm IL-22 can attenuate HSC activation and down-regulate the levels of inflammatory cytokines,thereby ameliorating liver fibrogenesis.
ISSN:1007-9327
2219-2840
DOI:10.3748/wjg.v21.i5.1531