title: Up-regulation of interleukin-22 mediates liver fibrosis via activating hepatic stellate cells in patients with hepatitis C.
abstract: Interleukin-22 (IL-22) is known to play a critical role in liver immunity. However, the role of IL-22 in HCV-associated liver fibrosis is poorly understood. In this study, patients with HCV infection disclosed significant increases in peripheral numbers of IL-22-producing cells as well as in IL-22 plasma levels. In the liver, the increased intrahepatic IL-22(+) cells were positively correlated with fibrotic staging scores and clinical progression from CHC to cirrhosis. Moreover, the majority of IL-22(+) cells were located in fibrotic areas in the liver of patients with cirrhosis and co-localized with α-smooth muscle actin (α-SMA) positive hepatic stellate cells (HSCs). In vitro, administration of IL-22 was accompanied with inhibited LX-2 cell apoptosis, promoted LX-2 cell proliferation, increased expression of α-SMA, and up-regulated collagen production by LX-2 cells. Collectively, our data provide evidence that IL-22 may contribute to the fibrogenesis of HCV-associated liver fibrosis by activating HSCs.
authors.affiliation: Department of Pathology and Hepatology, Beijing 302 Hospital, Beijing, China.
authors.forename: Li-Yuan
authors.initials: LY
authors.lastname: Wu
authors.affiliation: Department of Pathology and Hepatology, Beijing 302 Hospital, Beijing, China.
authors.forename: Shuhong
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Pathology and Hepatology, Beijing 302 Hospital, Beijing, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Pathology and Hepatology, Beijing 302 Hospital, Beijing, China.
authors.forename: Chaonan
authors.initials: C
authors.lastname: Guo
authors.affiliation: Liver Cirrhosis Diagnosis and Treatment Center, Beijing 302 Hospital, Beijing, China.
authors.forename: Hanwei
authors.initials: H
authors.lastname: Li
authors.affiliation: Center for Clinical Trial, Beijing 302 Hospital, Beijing, China.
authors.forename: Wenshu
authors.initials: W
authors.lastname: Li
authors.affiliation: International Center for Liver Disease Diagnosis and Treatment, Beijing 302 Hospital, Beijing, China.
authors.forename: Xueyuan
authors.initials: X
authors.lastname: Jin
authors.affiliation: Department of Hepatobiliary Surgery, Beijing 302 Hospital, Beijing, China.
authors.forename: Keming
authors.initials: K
authors.lastname: Zhang
authors.affiliation: International Center for Liver Disease Diagnosis and Treatment, Beijing 302 Hospital, Beijing, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhao
authors.affiliation: Liver Disease Research Center, Peking University People's Hospital, Beijing, China.
authors.forename: Lai
authors.initials: L
authors.lastname: Wei
authors.affiliation: Department of Pathology and Hepatology, Beijing 302 Hospital, Beijing, China. Electronic address: jmzhao302@163.com.
authors.forename: Jingmin
authors.initials: J
authors.lastname: Zhao
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000187:drug effects; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D016022:Case-Control Studies; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D055166:Hepatic Stellate Cells / Q000276:immunology*; D019698:Hepatitis C, Chronic / Q000209:etiology / Q000276:immunology*; D006801:Humans; D066298:In Vitro Techniques; D007378:Interleukins / Q000276:immunology* / Q000494:pharmacology; D008099:Liver / Q000166:cytology; D008103:Liver Cirrhosis / Q000209:etiology / Q000276:immunology*; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D015854:Up-Regulation; D055815:Young Adult; D000097043:Interleukin-22
chemical_list: D007378:Interleukins; D000097043:Interleukin-22
keywords: Hepatic stellate cell; Hepatitis C virus; Interleukin-22; Liver fibrosis