NDLI: Upregulation of IL-23 expression in patients with chronic hepatitis B is mediated by the HBx/ERK/NF-κB pathway.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Fan, Daiming Xia, Limin Zhu, Hongwu Zhang, Yongguo Tian, Dean Hu, Hao Huang, Wenjie Wang, Jing Nie, Yongzhan Wu, Kaichun
Description	Author Affiliation: Xia L ( State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, People's Republic of China.)
Abstract	IL-23 is a newly discovered proinflammatory cytokine that contributes to the maintenance and expansion of Th17 cells. IL-23 has recently been identified as playing a critical role in a number of chronic inflammatory diseases. However, the regulatory mechanism of IL-23 in chronic hepatitis B (CHB) remains largely unknown. The aims of this study were to detect the expression of IL-23 in CHB patients and to explore the molecular mechanism of hepatitis B virus (HBV)-induced IL-23 expression. Serum levels and hepatic expression of IL-23 were significantly upregulated in CHB patients. A positive correlation was found between IL-23 expression and the histological activity index score, HBV DNA load, and serum alanine aminotransferase and aspartate aminotransferase levels. HBx protein increased IL-23 expression in a dose-dependent manner. It also aided in the nuclear translocation of NF-κB, which directly bound to the promoters of IL-23 subunits p19 and p40 to facilitate their transcription. NF-κB inhibitors blocked the effect of HBx on IL-23 induction, and NF-κB subunits p65 and p50 increased the augmented IL-23 expression. Inhibition of ERK1/2 activation and transfection with ERK dominant-negative plasmid significantly blocked the HBx-induced IL-23 expression. Furthermore, PI3K and Ras-MEK-MAPK inhibitors significantly decreased the ERK1/2 activation and IL-23 expression. Thus, we report a new molecular mechanism for HBV-induced IL-23 expression, which involves the activation of the ERK/NF-κB pathway by HBx, leading to the transactivation of the IL-23 p19 and p40 promoters.
ISSN	00221767
e-ISSN	15506606
Journal	The Journal of Immunology
Issue Number	2
Volume Number	188
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2012-01-15
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Hepatitis B, Chronic Immunology Metabolism Interleukin-23 Biosynthesis Map Kinase Signaling System Nf-kappa B Physiology Signal Transduction Trans-activators Up-regulation Adolescent Hep G2 Cells Pathology Inflammation Mediators Antagonists & Inhibitors Blood Interleukin-12 Subunit P40 Genetics Interleukin-23 Subunit P19 Promoter Regions, Genetic Transcriptional Activation Research Support, Non-u.s. Gov't Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in