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 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).


CONCLUSION
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.
['Lu|Dong-Hong|DH|', 'Guo|Xiao-Yun|XY|', 'Qin|Shan-Yu|SY|', 'Luo|Wei|W|', 'Huang|Xiao-Li|XL|', 'Chen|Mei|M|', 'Wang|Jia-Xu|JX|', 'Ma|Shi-Jia|SJ|', 'Yang|Xian-Wen|XW|', 'Jiang|Hai-Xing|HX|']
D000818:Animals D000893:Anti-Inflammatory Agents D002251:Carbon Tetrachloride D016207:Cytokines D055166:Hepatic Stellate Cells D018836:Inflammation Mediators D007378:Interleukins D008099:Liver D008106:Liver Cirrhosis, Experimental D008297:Male D008807:Mice, Inbred BALB C D012333:RNA, Messenger D011994:Recombinant Proteins D012720:Severity of Illness Index D015398:Signal Transduction D018417:Th1 Cells D058504:Th17 Cells D013997:Time Factors
Interleukin-22 Hepatic fibrosis T helper 1 cells T helper 17 cells T helper 22 cells