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Downregulation of the AU-Rich RNA-Binding Protein ZFP36 in Chronic HBV Patients: Implications for Anti-Inflammatory Therapy
- Source :
- PLoS ONE, Vol 7, Iss 3, p e33356 (2012), PLoS ONE
- Publication Year :
- 2012
- Publisher :
- Public Library of Science (PLoS), 2012.
-
Abstract
- Inflammation caused by chronic hepatitis B virus (HBV) infection is associated with the development of cirrhosis and hepatocellular carcinoma; however, the mechanisms by which HBV infection induces inflammation and inflammatory cytokine production remain largely unknown. We analyzed the gene expression patterns of lymphocytes from chronic HBV-infected patients and found that the expression of ZFP36, an AU-rich element (ARE)-binding protein, was dramatically reduced in CD4(+) and CD8(+) T lymphocytes from chronic HBV patients. ZFP36 expression was also reduced in CD14(+) monocytes and in total PBMCs from chronic HBV patients. To investigate the functional consequences of reduced ZFP36 expression, we knocked down ZFP36 in PBMCs from healthy donors using siRNA. siRNA-mediated silencing of ZFP36 resulted in dramatically increased expression of multiple inflammatory cytokines, most of which were also increased in the plasma of chronic HBV patients. Furthermore, we found that IL-8 and RANTES induced ZFP36 downregulation, and this effect was mediated through protein kinase C. Importantly, we found that HBsAg stimulated PBMCs to express IL-8 and RANTES, resulting in decreased ZFP36 expression. Our results suggest that an inflammatory feedback loop involving HBsAg, ZFP36, and inflammatory cytokines may play a critical role in the pathogenesis of chronic HBV and further indicate that ZFP36 may be an important target for anti-inflammatory therapy during chronic HBV infection.
- Subjects :
- CD4-Positive T-Lymphocytes
Male
Viral Diseases
HBsAg
medicine.medical_treatment
lcsh:Medicine
CD8-Positive T-Lymphocytes
medicine.disease_cause
Hepatitis
Pathogenesis
Molecular Cell Biology
RNA, Small Interfering
lcsh:Science
Chemokine CCL5
Multidisciplinary
virus diseases
Middle Aged
Hepatitis B
Infectious Diseases
Cytokine
Gene Knockdown Techniques
Cytokines
Medicine
Female
medicine.symptom
Research Article
Adult
China
CD14
Immunology
Inflammation
Biology
Real-Time Polymerase Chain Reaction
Proinflammatory cytokine
Molecular Genetics
Tristetraprolin
Genetics
medicine
Humans
DNA Primers
Hepatitis B virus
Hepatitis B Surface Antigens
Interleukin-8
lcsh:R
Immunity
medicine.disease
digestive system diseases
Gene Expression Regulation
Leukocytes, Mononuclear
Clinical Immunology
lcsh:Q
Subjects
Details
- ISSN :
- 19326203
- Volume :
- 7
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....897bfa34bec80fa03c06a53060cd7a1f