Tumor Necrosis Factor Alpha Down-regulated Human GSTA1 and GSTA4 Expression Through The NF-κB Signaling Pathway in Human Hepatoma HepG2 Cells

Glutathione S-transferase Alphal and Alpha 4 (GSTA1 and GSTA4) are crucial for detoxifying a variety of endogenous and exogenous toxic compounds. However, GSTA1/4 expression is reduced in cholestatic patients. The molecular mechanism of GSTA1/4 down-regulation remains elusive. Here, we treated human hepatoma HepG2 cells with tumor necrosis factor alpha (TNF alpha) and measured the expression of GSTA 1/4, nuclear factor kappa B (NF-kappa B) and NF-E2 related factor 2 (Nrf2) by quantitative real-time quantitative polymerase chain reaction (qPCR) and Western blotting. We found that expression of GS'TA 1/4 was repressed by TNF alpha at both the mRNA and the protein level in a dose- and time-dependent manner. Furthermore, inhibiting the NF-kappa B signaling pathway could attenuate the TNF alpha induced reduction in GSTA1/4 expression in the HepG2 cells. Our findings indicate that down-regulation of GSTAI/4 expression in HepG2 cells is likely triggered by TNFa and mediated by activation of the NF-kappa B signaling pathway.