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hbsag Inhibits TLR2 Ligand-Induced IL-12 in Monocytes/Macrophages

J Immunol. 2013 Apr 12. [Epub ahead of print]
Hepatitis B Virus Surface Antigen Selectively Inhibits TLR2 Ligand-Induced IL-12 Production in Monocytes/Macrophages by Interfering with JNK Activation.
Wang S, Chen Z, Hu C, Qian F, Cheng Y, Wu M, Shi B, Chen J, Hu Y, Yuan Z.
Source
Key Laboratory of Medical Molecular Virology, Shanghai Public Health Clinical Center, Shanghai Medical College of Fudan University, Shanghai 200032, China;
Abstract
It is widely accepted that chronic hepatitis B virus (HBV) infection is the result of an ineffective antiviral immune response against HBV infection. Our previous study found that the hepatitis B surface Ag (HBsAg) was related to decreased cytokine production induced by the TLR2 ligand (Pam3csk4) in PBMCs from chronic hepatitis B patients. In this study, we further explored the mechanism involved in the inhibitory effect of HBsAg on the TLR2 signaling pathway. The results showed that both Pam3csk4-triggered IL-12p40 mRNA expression and IL-12 production in PMA-differentiated THP-1 macrophage were inhibited by HBsAg in a dose-dependent manner, but the production of IL-1β, IL-6, IL-8, IL-10, and TNF-α was not influenced. The Pam3csk4-induced activation of NF-κB and MAPK signaling were further examined. The phosphorylation of JNK-1/2 and c-Jun was impaired in the presence of HBsAg, whereas the degradation of IκB-α, the nuclear translocation of p65, and the phosphorylation of p38 and ERK-1/2 were not affected. Moreover, the inhibition of JNK phosphorylation and IL-12 production in response to Pam3csk was observed in HBsAg-treated monocytes/macrophages (M/MΦs) from the healthy donors and the PBMCs and CD14-positive M/MΦs from chronic hepatitis B patients. Taken together, these results demonstrate that HBsAg selectively inhibits Pam3csk4- stimulated IL-12 production in M/MΦs by blocking the JNK-MAPK pathway and provide a mechanism by which HBV evades immunity and maintains its persistence.
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Avatar universal
Thanks for your research sharing and comments , If you have idea that could i pass in medical exams for immigration. It will be really take out me from mental stress and tension.

Here i would like to share that in case of any discrepancy in medical reports DIAC Australia refereed this case to MOC(Medical Officer Commonwealth). The decision will finalized by panel of MOC.

Kindly share any appropriate knowledge if you have, as you are experience medical professionals and must faced any correlated case.

Kind Regards,
Misbah    

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Avatar universal
Well done research that used surface antigen concentrations that are expected in chronic patients. 1, 5, and 25 microgram/ml, which is approx equivalent to 1000iU, 5000, and 2500 iU/ml.

At 1 ug/ml there was almost no neg effect on Il-12 production, at 5 there was an approx 30% decrease and up to 80% less Il-12 was produced in the presence of 25 ug/ml. Overall this points to yet another mechanism by which high  surface antigen impairs the generation of an effective Tcell response of the Th-1 kind, which mainly focuses on CTL production and ultimately gamma interferon release to clear cccDNA from infected hepatocytes.
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