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Interleukin-22 ameliorates liver fibrogenesis by attenuating hepatic stellate cell activation and downregulating the levels of inflammatory cytokines #MMPMID25663772
Lu DH; Guo XY; Qin SY; Luo W; Huang XL; Chen M; Wang JX; Ma SJ; Yang XW; Jiang HX
World J Gastroenterol 2015[Feb]; 21 (5): 1531-45 PMID25663772show ga
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 CCl(4). Recombinant IL-22 (rmIL-22) was administered intraperitoneally in CCl(4)-treated mice. Fibrosis was assessed by histology and Masson staining. The activation of hepatic stellate cells (HSCs) was investigated by analysis of alpha-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-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), IL-6, IL-1beta] and transcription factors [aryl hydrocarbon receptor (AHR), RAR-related orphan receptor (RORgammat), T-bet] mRNA in the liver were investigated. In addition, the plasma levels of IL-22, IL-17A, IFN-gamma, TNF-alpha, IL-6 and IL-1beta were evaluated. RESULTS: Significant elevations in circulating Th22 cells, Th17 cells, Th1 cells, IL-22, IL-17A, and IFN-gamma 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-gamma (74.78 +/- 2.61 vs 124.89 +/- 2.82, P < 0.01). Down-regulation of IL-22, IL-17A, IFN-gamma, TNF-alpha, IL-6, IL-1beta, AHR RORgammat, 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.
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World+J+Gastroenterol 2015 ; 21 (5): 1531-45
