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Regulation of Toll‐like receptor‐2 expression in chronic hepatitis B by the precore protein
Author(s) -
Visvanathan Kumar,
Skinner Narelle A.,
Thompson Alex J.V.,
Riordan Stephen M.,
Sozzi Vitini,
Edwards Roslyn,
Rodgers Sally,
Kurtovic Jelica,
Chang Judy,
Lewin Sharon,
Desmond Paul,
Locarnini Stephen
Publication year - 2007
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.21482
Subject(s) - hbeag , tlr2 , hepatitis b virus , innate immune system , immunology , virology , medicine , receptor , tlr4 , immune system , biology , virus , hbsag
Toll‐like receptors (TLRs) play a key role in the innate immune response. The aim of this study was to examine the expression of TLR2 and TLR4 in chronic hepatitis B (CHB). The TLR2 and TLR4 expression on hepatocytes and Kupffer cells from fresh liver biopsies was measured from 21 patients with untreated hepatitis B e antigen (HBeAg)‐positive and HBeAg‐negative CHB. Parallel studies were also undertaken on monocytes from their peripheral blood. Expression of TLR2 on hepatocytes, Kupffer cells, and peripheral monocytes was significantly reduced in patients with HBeAg‐positive CHB in comparison with HBeAg‐negative CHB and controls, whereas it was significantly increased in HBeAg‐negative CHB compared with controls. The level of TLR4 expression did not differ significantly between the groups. These results were confirmed in vitro using hepatic cell lines transduced with recombinant HBV baculovirus expressing wild‐type HBV (HBeAg‐positive), precore stop codon (G1896A) mutant HBV (HBeAg‐negative). The functional relevance of these findings was established by the demonstration of significantly reduced cytokine production (TNF‐α) and phospho‐p38 kinase expression in the presence of the HBeAg. In the absence of HBeAg, HBV replication was associated with up‐regulation of the TLR2 pathway leading to increased TNF‐α production. Conclusion : This study demonstrates a potentially important interaction between HBeAg, HBV, and the innate immune response. (H EPATOLOGY 2007;45:102–110.)