Downregulation of the AU-rich RNA-binding protein ZFP36 in chronic HBV patients: implications for anti-inflammatory therapy.

摘要: Inflammation caused by chronic hepatitis B virus (HBV) infection is associated with the development of cirrhosis and hepatocellular carcinoma; however, mechanisms which HBV induces inflammation inflammatory cytokine production remain largely unknown. We analyzed gene expression patterns lymphocytes from HBV-infected patients found that ZFP36, an AU-rich element (ARE)-binding protein, was dramatically reduced in CD4+ CD8+ T patients. ZFP36 also CD14+ monocytes total PBMCs To investigate functional consequences expression, we knocked down healthy donors using siRNA. siRNA-mediated silencing resulted increased multiple cytokines, most were plasma Furthermore, IL-8 RANTES induced downregulation, this effect mediated through protein kinase C. Importantly, HBsAg stimulated to express RANTES, resulting decreased expression. Our results suggest feedback loop involving HBsAg, cytokines may play a critical role pathogenesis further indicate be important target for anti-inflammatory therapy during infection.