Toll-like Receptor-2 Expression in Patients with Chronic Hepatitis B

Toll-like receptors (TLRs) play a key role in the innate immune response, and agents that block TLR activity are under study as experimental therapies for viral hepatitis.

In a study reported in the January 2007 issue of Hepatology, researchers examined the expression of TLR2 and TLR4 in patients with chronic hepatitis B. TLR2 and TLR4 expression was measured on hepatocytes and Kupffer cells from fresh liver biopsies from 21 patients with untreated hepatitis B "e" antigen (HBeAg) positive and HBeAg negative chronic hepatitis B. Parallel studies were undertaken on monocytes from the same patients' peripheral blood.

Results

• Expression of TLR2 on hepatocytes, Kupffer cells, and peripheral blood monocytes was significantly reduced in patients with HBeAg positive chronic hepatitis B compared with HBeAg negative subjects.

• TLR2 expression was significantly increased in HBeAg negative chronic hepatitis B patients compared with control subjects.


• 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) and precore stop codon (G1896A) mutant HBV (HBeAg-negative).

• The functional relevance of these findings was established by demonstrating significantly reduced TNF-alpha production and phospho-p38 kinase expression in the presence of HBeAg.

• In the absence of HBeAg, HBV replication was associated with up-regulation of the TLR2 pathway leading to increased TNF-alpha production.

Conclusion

"This study demonstrates a potentially important interaction between HBeAg, HBV, and the innate immune response," the researchers concluded.

1/12/07

Reference
K Visvanathan, N A Skinner, A J Thompson, and others. Regulation of Toll-like receptor-2 expression in chronic hepatitis B by the precore protein. Hepatology 45(1): 102-110. January 2007.