Tumor necrosis factor alpha (TNF-α) appears to play an important role in proliferation and activation of hepatic stellate cells (HSCs), but it is unclear whether single nucleotide polymorphisms (SNPs) in the TNF-α gene influence HSCs function. In this study, we explored the effects of TNF-α A94T and P84L polymorphisms on the level of TNF-α, proliferation and activation of HSCs. It was found that A94T and P84L SNPs of TNF-α downregulated the mRNA and protein level of TNF-α in recombinant cells. Compared with wild-type TNF-α, A94T and P84L SNPs could decrease the growth or activation inhibitory effects of TNF-α on LX-2 cells, the human HSC line. In addition, A94T SNPs were associated with significantly lower expression of matrix-metalloproteinase 2 (MMP 2) or 9, but P84L SNP only decreased the mRNA level of MMP 9. A94T and P84L SNPs of TNF-α downregulated the level of IL-6. Furthermore, A94T and P84L SNPs decrease the activation inhibitory effects of TNF-α on LX-2 cells through inhibiting the phosphorylation levels of inhibitory kappa B-alpha (IκB-α) and P65. This study provides two vital SNPs for further functional or case–control studies of TNF-α SNPs.
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