Interleukin-21 mediates hepatitis B virus-associated liver cirrhosis by activating hepatic stellate cells

• Published in: Hepatology research Vol. 44; no. 10; pp. E198 - E205
• Main Authors: Feng, Guohua, Zhang, Ji-Yuan, Zeng, Qing-Lei, Yu, Xi, Zhang, Zheng, Lv, Sa, Xu, Xiangsheng, Wang, Fu-Sheng
• Format: Journal Article
• Language: English
• Published: Netherlands Blackwell Publishing Ltd 01.10.2014
• Subjects: hepatic stellate cell; hepatitis B virus-associated liver cirrhosis; interleukin-21; interleukin-21; hepatic stellate cell; hepatitis B virus-associated liver cirrhosis
• ISSN: 1386-6346; 1872-034X
• DOI: 10.1111/hepr.12215

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.