title: SOCS3 expression correlates with severity of inflammation in mouse hepatitis virus strain 3-induced acute liver failure and HBV-ACLF.
abstract: Recently, suppressor of cytokine signaling-3 (SOCS3) has been shown to be an inducible endogenous negative regulator of Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway which is relevant in inflammatory response, while its functions in acute liver failure and HBV-induced acute-on-chronic liver failure (HBV-ACLF) have not been fully elucidated. In this study, we explored the role of SOCS3 in the development of mouse hepatitis virus strain 3 (MHV-3)-induced acute liver failure and its expression in liver and peripheral blood mononuclear cells (PBMCs) of patients with HBV-ACLF. Inflammation-related gene expression was detected by real-time PCR, immunohistochemistry and Western blotting. The correlation between SOCS3 level and liver injury was studied. Our results showed that the SOCS3 expression was significantly elevated in both the liver tissue and PBMCs from patients with HBV-ACLF compared to mild chronic hepatitis B (CHB). Moreover, a time course study showed that SOCS3 level was increased remarkably in the liver of BALB/cJ mice at 72 h post-infection. Pro-inflammatory cytokines, interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α, were also increased significantly at 72 h post-infection. There was a close correlation between hepatic SOCS3 level and IL-6, and the severity of liver injury defined by alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, respectively. These data suggested that SOCS3 may play a pivotal role in the pathogenesis of MHV-3-induced acute liver failure and HBV-ACLF.
authors.affiliation: Department and Institute of Infectious Diseases, University of Science and Technology, Wuhan, 430030, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department and Institute of Infectious Diseases, University of Science and Technology, Wuhan, 430030, China.
authors.forename: Mei-Fang
authors.initials: MF
authors.lastname: Han
authors.affiliation: Department and Institute of Infectious Diseases, University of Science and Technology, Wuhan, 430030, China.
authors.forename: Wei-Na
authors.initials: WN
authors.lastname: Li
authors.affiliation: Department and Institute of Infectious Diseases, University of Science and Technology, Wuhan, 430030, China.
authors.forename: Ai-Chao
authors.initials: AC
authors.lastname: Shi
authors.affiliation: Department and Institute of Infectious Diseases, University of Science and Technology, Wuhan, 430030, China.
authors.forename: Yuan-Ya
authors.initials: YY
authors.lastname: Zhang
authors.affiliation: Department and Institute of Infectious Diseases, University of Science and Technology, Wuhan, 430030, China.
authors.forename: Hong-Yan
authors.initials: HY
authors.lastname: Wang
authors.affiliation: Department and Institute of Infectious Diseases, University of Science and Technology, Wuhan, 430030, China.
authors.forename: Fa-Xi
authors.initials: FX
authors.lastname: Wang
authors.affiliation: Department and Institute of Infectious Diseases, University of Science and Technology, Wuhan, 430030, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Li
authors.affiliation: Department and Institute of Infectious Diseases, University of Science and Technology, Wuhan, 430030, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Wu
authors.affiliation: Department and Institute of Infectious Diseases, University of Science and Technology, Wuhan, 430030, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Ding
authors.affiliation: Department and Institute of Infectious Diseases, University of Science and Technology, Wuhan, 430030, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Chen
authors.affiliation: Department and Institute of Infectious Diseases, University of Science and Technology, Wuhan, 430030, China.
authors.forename: Wei-Ming
authors.initials: WM
authors.lastname: Yan
authors.affiliation: Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong, University of Science and Technology, Wuhan, 430030, China.
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Luo
authors.affiliation: Department and Institute of Infectious Diseases, University of Science and Technology, Wuhan, 430030, China. qning@vip.sina.com.
authors.forename: Qin
authors.initials: Q
authors.lastname: Ning
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D015153:Blotting, Western; D058625:End Stage Liver Disease / Q000235:genetics / Q000473:pathology / Q000821:virology*; D005260:Female; D015870:Gene Expression; D006524:Hepatitis, Viral, Animal / Q000235:genetics / Q000473:pathology / Q000821:virology*; D054884:Host-Pathogen Interactions; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000821:virology; D017114:Liver Failure, Acute / Q000235:genetics / Q000473:pathology / Q000821:virology*; D008297:Male; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D006517:Murine hepatitis virus / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012720:Severity of Illness Index; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: D053583:Interleukin-1beta; D015850:Interleukin-6; C106644:SOCS3 protein, human; C491411:Socs3 protein, mouse; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D014409:Tumor Necrosis Factor-alpha; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase