Blockage of Notch1 signaling modulates the T-helper (Th)1/Th2 cell balance in chronic hepatitis B patients

Hepatol Res. 2010 Aug;40(8):799-805. doi: 10.1111/j.1872-034X.2010.00680.x. Epub 2010 Jul 7.

Abstract

Aim: Chronic hepatitis B virus (HBV) infection is thought to involve the imbalance of T-helper (Th)1/Th2 cells. Many procedures found Notch signaling involved the proliferation and differentiation of T lymphocytes during development and peripheral functions. The aim of this study was to discover the effect of blockage of Notch1 signaling to Th cells and the mechanisms involved in chronic hepatitis B patients.

Methods: CD4(+) T cells from hepatitis B patients and healthy volunteers were isolated, and Notch1 expression of CD4(+) T cells was determined by reverse transcription polymerase chain reaction (RT-PCR). Blockage of Notch1 signaling of peripheral blood mononuclear cells (PBMC) from chronic hepatitis B patients, Th1- and Th2-type cytokines were assayed by enzyme-linked immunosorbent assay and levels of T-bet, GATA-3 mRNA were measured by RT-PCR.

Results: Notch1 expression of CD4(+) T cells from chronic hepatitis B patients was upregulated, on the contrary to that from acute hepatitis B patients and healthy volunteers. Blockage of Notch1 signaling can strongly inhibit the production of Th2-type cytokines and the expression of GATA-3; the production of Th1-type cytokines and the expression of T-bet, however, were enhanced.

Conclusion: Blockage of Notch1 signaling could regulate the immune balance of Th1/Th2 in chronic hepatitis B patients, which may be mediated partly by regulating transcription factors T-bet and GATA-3.