title: Up-regulation of IL-12 expression in patients with chronic hepatitis B is mediated by the PI3K/Akt pathway.
abstract: Hepatitis B virus (HBV) replicates noncytopathically in hepatocytes, but HBV or proteins encoded by HBV genome could induce cytokines, chemokines expression by hepatocytes.IL-12 is a typical proinflammatory cytokine that plays a critical role in host defense against pathogens, including the HBV. However, the role of IL-12 in chronic hepatitis B (CHB) remains unclear. The aims of this study were to detect the expression of IL-12 in CHB patients and explore the molecular mechanism of HBV-induced IL-12 expression. The results showed that serum levels and hepatic expression of IL-12 were significantly upregulated in CHB patients. HBx protein increased IL-12 expression in a dose-dependent manner. Furthermore, inhibition of PI3K/Akt significantly decreased the HBx-induced IL-12 expression and Akt activation. Taken together, these results indicate that the molecular mechanism of HBV-induced IL-12 expression involves activation of the PI3K/Akt pathway by HBx, leading to transactivation of the IL-12 p35 and p40 promoters.
authors.affiliation: Department of Infection Diseases, The First Affiliated Hospital of Xinxiang Medical University, Weihui, 453100, China.
authors.forename: Hong-wei
authors.initials: HW
authors.lastname: Wang
authors.forename: Hai-li
authors.initials: HL
authors.lastname: Gao
authors.forename: Xiao-xia
authors.initials: XX
authors.lastname: Wei
authors.forename: Xin-hong
authors.initials: XH
authors.lastname: Wang
mesh_terms: D000328:Adult; D002460:Cell Line; D005260:Female; D056945:Hep G2 Cells; D006515:Hepatitis B virus / Q000378:metabolism; D019694:Hepatitis B, Chronic / Q000097:blood / Q000235:genetics / Q000276:immunology*; D006801:Humans; D053765:Interleukin-12 Subunit p35 / Q000378:metabolism*; D053762:Interleukin-12 Subunit p40 / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D015534:Trans-Activators / Q000276:immunology*; D015854:Up-Regulation; D054334:Viral Regulatory and Accessory Proteins; D055815:Young Adult
chemical_list: D053765:Interleukin-12 Subunit p35; D053762:Interleukin-12 Subunit p40; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C508858:IL12A protein, human; C500879:IL12B protein, human; C057628:hepatitis B virus X protein