title: IL-17A but not IL-22 suppresses the replication of hepatitis B virus mediated by over-expression of MxA and OAS mRNA in the HepG2.2.15 cell line.
abstract: Interleukin-17A (IL-17A) and interleukin-22 (IL-22), mainly secreted by interleukin-17-producing T help cells (Th17), are pleiotropic cytokines that regulate the biological responses of several target cells, including hepatocytes. Th17 frequency was reported to negatively correlate with plasma hepatitis B virus (HBV) DNA load in patients with HBV infection. Several studies have indicated that cytokines, such as IL-6 and IL-4, are involved in the noncytopathic suppression of HBV replication. We therefore hypothesized that IL-17A and IL-22 might have a potent suppressive effect on HBV replication. In our present study, we analyzed the suppressive effect of IL-17A and IL-22 on HBV replication in the hepatocellular carcinoma cell line HepG2.2.15. IL-17A did not inhibit the proliferation of HepG2.2.15 cells. It decreased the levels of HBV s antigen (HBsAg) and HBV e antigen (HBeAg) in culture medium and the levels of intracellular HBV DNA. By contrast, blockage of IL-17 receptor (IL-17R) increased the levels of HBsAg and extracellular HBV DNA in culture medium and the levels of intracellular HBV DNA. The expression of antiviral proteins, including myxovirus resistance A (MxA) and oligoadenylate synthetase (OAS), was enhanced by IL-17A. IL-22 and anti-human IL-22 receptor (IL-22R) antibody did not change any indexes. We demonstrated that IL-17A effectively suppressed HBV replication in a noncytopathic manner and the over-expression of MxA and OAS mRNA was involved in the suppression of HBV replication by IL-17A.
authors.affiliation: Department of Hepatology, Qilu Hospital of Shandong University, Wenhuaxi Road 107#, Jinan 250012, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Wang
authors.forename: Xin-Ping
authors.initials: XP
authors.lastname: Zhao
authors.forename: Yu-Chen
authors.initials: YC
authors.lastname: Fan
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Zhang
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
mesh_terms: D015088:2',5'-Oligoadenylate Synthetase / Q000235:genetics* / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000821:virology*; D015536:Down-Regulation; D019204:GTP-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D006515:Hepatitis B virus / Q000235:genetics / Q000502:physiology*; D006801:Humans; D020381:Interleukin-17 / Q000378:metabolism*; D007378:Interleukins / Q000378:metabolism*; D064547:Myxovirus Resistance Proteins; D015854:Up-Regulation; D014779:Virus Replication; D000097043:Interleukin-22
chemical_list: D015088:2',5'-Oligoadenylate Synthetase; D019204:GTP-Binding Proteins; D020381:Interleukin-17; D007378:Interleukins; D064547:Myxovirus Resistance Proteins; D000097043:Interleukin-22; C579071:MX1 protein, human; C475085:OAS1 protein, human