Interleukin-21 mediates hepatitis B virus-associated liver cirrhosis by activating hepatic stellate cells
Aim Interleukin‐21 (IL‐21) is involved in effective primary hepatic immune response against hepatitis B virus (HBV) and profibrotic function. However, the role of IL‐21 in HBV‐associated liver cirrhosis is poorly understood. This study aimed to investigate the role of IL‐21 in HBV‐associated liver c...
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| Published in | Hepatology research Vol. 44; no. 10; pp. E198 - E205 |
|---|---|
| Main Authors | , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Netherlands
Blackwell Publishing Ltd
01.10.2014
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| Subjects | |
| Online Access | Get full text |
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| Abstract | Aim
Interleukin‐21 (IL‐21) is involved in effective primary hepatic immune response against hepatitis B virus (HBV) and profibrotic function. However, the role of IL‐21 in HBV‐associated liver cirrhosis is poorly understood. This study aimed to investigate the role of IL‐21 in HBV‐associated liver cirrhosis and possible mechanisms.
Methods
The study subjects included 10 healthy controls and 30 patients with HBV‐associated liver cirrhosis that categorized into three subgroups based on Child–Pugh score (A, 13; B, 10; C, 7). The frequencies of IL‐21+CD4+ T cells were detected by flow cytometry, and the level of IL‐21 in plasma was measured by enzyme‐linked immunoassay. The distribution of IL‐21+ cells in situ in liver was observed by immunohistochemistry. In addition, the in vitro expression of α‐smooth muscle actin (α‐SMA), apoptosis and proliferation markers of LX‐2 cells were examined by flow cytometry and Cell Counting Kit‐8 kit. Finally, the collagen levels in the supernatant were measured by chemiluminescence.
Results
Increased peripheral number of IL‐21+CD4+ cells, elevated plasma level of IL‐21 and IL‐21+ cell accumulation in liver were observed in patients with HBV‐associated liver cirrhosis. In vitro administration of IL‐21 was accompanied with increased expression of α‐SMA, inhibited LX‐2 cells apoptosis and upregulated collagen production by LX‐2 cells.
Conclusion
IL‐21 may contribute to the fibrogenesis of HBV‐associated liver cirrhosis by activating the hepatic stellate cells. Therefore, neutralization of IL‐21 could be a favorable new therapeutic strategy for liver cirrhosis treatment. |
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| AbstractList | Interleukin-21 (IL-21) is involved in effective primary hepatic immune response against hepatitis B virus (HBV) and profibrotic function. However, the role of IL-21 in HBV-associated liver cirrhosis is poorly understood. This study aimed to investigate the role of IL-21 in HBV-associated liver cirrhosis and possible mechanisms.
The study subjects included 10 healthy controls and 30 patients with HBV-associated liver cirrhosis that categorized into three subgroups based on Child-Pugh score (A, 13; B, 10; C, 7). The frequencies of IL-21(+) CD4(+) T cells were detected by flow cytometry, and the level of IL-21 in plasma was measured by enzyme-linked immunoassay. The distribution of IL-21(+) cells in situ in liver was observed by immunohistochemistry. In addition, the in vitro expression of α-smooth muscle actin (α-SMA), apoptosis and proliferation markers of LX-2 cells were examined by flow cytometry and Cell Counting Kit-8 kit. Finally, the collagen levels in the supernatant were measured by chemiluminescence.
Increased peripheral number of IL-21(+) CD4(+) cells, elevated plasma level of IL-21 and IL-21(+) cell accumulation in liver were observed in patients with HBV-associated liver cirrhosis. In vitro administration of IL-21 was accompanied with increased expression of α-SMA, inhibited LX-2 cells apoptosis and upregulated collagen production by LX-2 cells.
IL-21 may contribute to the fibrogenesis of HBV-associated liver cirrhosis by activating the hepatic stellate cells. Therefore, neutralization of IL-21 could be a favorable new therapeutic strategy for liver cirrhosis treatment. Aim Interleukin‐21 (IL‐21) is involved in effective primary hepatic immune response against hepatitis B virus (HBV) and profibrotic function. However, the role of IL‐21 in HBV‐associated liver cirrhosis is poorly understood. This study aimed to investigate the role of IL‐21 in HBV‐associated liver cirrhosis and possible mechanisms. Methods The study subjects included 10 healthy controls and 30 patients with HBV‐associated liver cirrhosis that categorized into three subgroups based on Child–Pugh score (A, 13; B, 10; C, 7). The frequencies of IL‐21+CD4+ T cells were detected by flow cytometry, and the level of IL‐21 in plasma was measured by enzyme‐linked immunoassay. The distribution of IL‐21+ cells in situ in liver was observed by immunohistochemistry. In addition, the in vitro expression of α‐smooth muscle actin (α‐SMA), apoptosis and proliferation markers of LX‐2 cells were examined by flow cytometry and Cell Counting Kit‐8 kit. Finally, the collagen levels in the supernatant were measured by chemiluminescence. Results Increased peripheral number of IL‐21+CD4+ cells, elevated plasma level of IL‐21 and IL‐21+ cell accumulation in liver were observed in patients with HBV‐associated liver cirrhosis. In vitro administration of IL‐21 was accompanied with increased expression of α‐SMA, inhibited LX‐2 cells apoptosis and upregulated collagen production by LX‐2 cells. Conclusion IL‐21 may contribute to the fibrogenesis of HBV‐associated liver cirrhosis by activating the hepatic stellate cells. Therefore, neutralization of IL‐21 could be a favorable new therapeutic strategy for liver cirrhosis treatment. Interleukin-21 (IL-21) is involved in effective primary hepatic immune response against hepatitis B virus (HBV) and profibrotic function. However, the role of IL-21 in HBV-associated liver cirrhosis is poorly understood. This study aimed to investigate the role of IL-21 in HBV-associated liver cirrhosis and possible mechanisms.AIMInterleukin-21 (IL-21) is involved in effective primary hepatic immune response against hepatitis B virus (HBV) and profibrotic function. However, the role of IL-21 in HBV-associated liver cirrhosis is poorly understood. This study aimed to investigate the role of IL-21 in HBV-associated liver cirrhosis and possible mechanisms.The study subjects included 10 healthy controls and 30 patients with HBV-associated liver cirrhosis that categorized into three subgroups based on Child-Pugh score (A, 13; B, 10; C, 7). The frequencies of IL-21(+) CD4(+) T cells were detected by flow cytometry, and the level of IL-21 in plasma was measured by enzyme-linked immunoassay. The distribution of IL-21(+) cells in situ in liver was observed by immunohistochemistry. In addition, the in vitro expression of α-smooth muscle actin (α-SMA), apoptosis and proliferation markers of LX-2 cells were examined by flow cytometry and Cell Counting Kit-8 kit. Finally, the collagen levels in the supernatant were measured by chemiluminescence.METHODSThe study subjects included 10 healthy controls and 30 patients with HBV-associated liver cirrhosis that categorized into three subgroups based on Child-Pugh score (A, 13; B, 10; C, 7). The frequencies of IL-21(+) CD4(+) T cells were detected by flow cytometry, and the level of IL-21 in plasma was measured by enzyme-linked immunoassay. The distribution of IL-21(+) cells in situ in liver was observed by immunohistochemistry. In addition, the in vitro expression of α-smooth muscle actin (α-SMA), apoptosis and proliferation markers of LX-2 cells were examined by flow cytometry and Cell Counting Kit-8 kit. Finally, the collagen levels in the supernatant were measured by chemiluminescence.Increased peripheral number of IL-21(+) CD4(+) cells, elevated plasma level of IL-21 and IL-21(+) cell accumulation in liver were observed in patients with HBV-associated liver cirrhosis. In vitro administration of IL-21 was accompanied with increased expression of α-SMA, inhibited LX-2 cells apoptosis and upregulated collagen production by LX-2 cells.RESULTSIncreased peripheral number of IL-21(+) CD4(+) cells, elevated plasma level of IL-21 and IL-21(+) cell accumulation in liver were observed in patients with HBV-associated liver cirrhosis. In vitro administration of IL-21 was accompanied with increased expression of α-SMA, inhibited LX-2 cells apoptosis and upregulated collagen production by LX-2 cells.IL-21 may contribute to the fibrogenesis of HBV-associated liver cirrhosis by activating the hepatic stellate cells. Therefore, neutralization of IL-21 could be a favorable new therapeutic strategy for liver cirrhosis treatment.CONCLUSIONIL-21 may contribute to the fibrogenesis of HBV-associated liver cirrhosis by activating the hepatic stellate cells. Therefore, neutralization of IL-21 could be a favorable new therapeutic strategy for liver cirrhosis treatment. |
| Author | Wang, Fu-Sheng Feng, Guohua Zhang, Zheng Yu, Xi Xu, Xiangsheng Zeng, Qing-Lei Zhang, Ji-Yuan Lv, Sa |
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| References_xml | – reference: Friedman SL. Mechanisms of hepatic fibrogenesis. Gastroenterology 2008; 134: 1655-1669. – reference: Parrish-Novak J, Dillon SR, Nelson A et al. Interleukin 21 and its receptor are involved in NK cell expansion and regulation of lymphocyte function. Nature 2000; 408: 57-63. – reference: Ma SW, Huang X, Li YY et al. High serum IL-21 levels after 12 weeks of antiviral therapy predict HBeAg seroconversion in chronic hepatitis B. J Hepatol 2012; 56: 775-781. – reference: Hu X, Ma S, Huang X et al. Interleukin-21 is upregulated in hepatitis B-related acute-on-chronic liver failure and associated with severity of liver disease. J Viral Hepat 2011; 18: 458-467. – reference: Rehermann B, Nascimbeni M. Immunology of hepatitis B virus and hepatitis C virus infection. Nat Rev Immunol 2005; 5: 215-229. – reference: Tritto G, Bechlis Z, Stadlbauer V et al. Evidence of neutrophil functional defect despite inflammation in stable cirrhosis. J Hepatol 2011; 55: 574-581. – reference: Monteleone G, Pallone F, MacDonald TT. Interleukin-21: a critical regulator of the balance between effector and regulatory T-cell responses. Trends Immunol 2008; 29: 290-294. – reference: Pesce J, Kaviratne M, Ramalingam TR et al. The IL-21 receptor augments Th2 effector function and alternative macrophage activation. J Clin Invest 2006; 116: 2044-2055. – reference: Friedman SL. Hepatic stellate cells: protean, multifunctional, and enigmatic cells of the liver. Physiol Rev 2008; 88: 125-172. – reference: Duffield JS, Forbes SJ, Constandinou CM et al. Selective depletion of macrophages reveals distinct, opposing roles during liver injury and repair. J Clin Invest 2005; 115: 56-65. – reference: Publicover J, Goodsell A, Nishimura S et al. IL-21 is pivotal in determining age-dependent effectiveness of immune responses in a mouse model of human hepatitis B. J Clin Invest 2011; 121: 1154-1162. – reference: Spolski R, Leonard WJ. 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| Title | Interleukin-21 mediates hepatitis B virus-associated liver cirrhosis by activating hepatic stellate cells |
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