1. Roles of TIPE2 in hepatitis B virus-induced hepatic inflammation in humans and mice.
- Author
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Xi W, Hu Y, Liu Y, Zhang J, Wang L, Lou Y, Qu Z, Cui J, Zhang G, Liang X, Ma C, Gao C, Chen Y, and Liu S
- Subjects
- Adolescent, Adult, Animals, Case-Control Studies, Child, Disease Models, Animal, Down-Regulation, Female, Hepatitis B, Chronic genetics, Humans, Intracellular Signaling Peptides and Proteins deficiency, Intracellular Signaling Peptides and Proteins genetics, Leukocytes, Mononuclear metabolism, Liver metabolism, Male, Mice, Mice, Inbred C57BL, Middle Aged, RNA, Messenger genetics, RNA, Messenger metabolism, Hepatitis B virus physiology, Hepatitis B, Chronic virology, Intracellular Signaling Peptides and Proteins metabolism, Liver pathology, Liver virology
- 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., (Copyright © 2011 Elsevier Ltd. All rights reserved.)
- Published
- 2011
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