title: Roles of TIPE2 in hepatitis B virus-induced hepatic inflammation in humans and mice.
abstract: Hepatitis B virus (HBV)-induced hepatic inflammation afflicts hundreds of millions of people worldwide and is a leading cause of hepatic cancer. While the deleterious effect of the chronic hepatitis is well recognized, the molecular mechanisms underlying the pathogenesis of HBV-induced hepatic inflammation are not well understood. We report here that the tumor necrosis factor-alpha-induced protein-8 like-2 (TIPE2 or TNFAIP8L2), a newly identified regulator of immune receptor signaling, plays an important role in controlling HBV-induced hepatitis. Patients with chronic hepatitis B had significantly reduced levels of TIPE2 expression in their peripheral blood mononuclear cells (PBMCs) as compared to healthy individuals. The TIPE2 expression negatively correlated with the blood levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (Tbil) as well as the HBV load of the patients. Importantly, using a murine model of HBV-induced hepatitis, we found that TIPE2-deficient mice developed significantly more severe hepatic inflammation than wild type mice. These results indicate that TIPE2 plays an important role in taming HBV-induced hepatic inflammation.
authors.affiliation: Institute of Immunology, Shandong University School of Medicine, PR China.
authors.forename: Wenjin
authors.initials: W
authors.lastname: Xi
authors.forename: Yejia
authors.initials: Y
authors.lastname: Hu
authors.forename: Yugang
authors.initials: Y
authors.lastname: Liu
authors.forename: Jiao
authors.initials: J
authors.lastname: Zhang
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Yunwei
authors.initials: Y
authors.lastname: Lou
authors.forename: Zhonghua
authors.initials: Z
authors.lastname: Qu
authors.forename: Jian
authors.initials: J
authors.lastname: Cui
authors.forename: Guizhong
authors.initials: G
authors.lastname: Zhang
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Liang
authors.forename: Chunhong
authors.initials: C
authors.lastname: Ma
authors.forename: Chengjiang
authors.initials: C
authors.lastname: Gao
authors.forename: Youhai
authors.initials: Y
authors.lastname: Chen
authors.forename: Suxia
authors.initials: S
authors.lastname: Liu
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D016022:Case-Control Studies; D002648:Child; D004195:Disease Models, Animal; D015536:Down-Regulation; D005260:Female; D006515:Hepatitis B virus / Q000502:physiology*; D019694:Hepatitis B, Chronic / Q000235:genetics / Q000821:virology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology* / Q000821:virology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D012333:RNA, Messenger; C529002:TIPE2 protein, mouse; C552057:TNFAIP8L2 protein, human