Toll样受体4在二氧化硅诱导巨噬细胞肿瘤坏死因子α合成中的作用

Objective To characterize the role of Toll-like receptor 4 (TLR4) in silica-induced pro-duction of tumor necrosis factor α(TNFα) from macrophage cell line. Methods The human macrophage cell line THP-1 was incubated with silica suspension. Cell media were collected and TNFα levels in the super-natants measured with ELJSA. To examine the involvement of TLR4 in silica-induced TNFα release, the neu-tralizing antibody (HTA125) against human TLR4 receptor was employed topretreat THP-1 cells prior to silica treatment. Moreover, murine macrophages expressing wild type or mutated TLR4 were also treated with silica to verify the effect of TLR4 in silica-induced TNFα release. Results Compared with the control group[(3.18± 0.41) pg/ml], the TNFα release in cells exposed to 100 μg/ml silica for 4 h and 8 h [(4.71±0.84),(6.22±0.58) pg/ml, respectively] increased 1.48 and 1.96 fold, respectively. Pretreatment of THP-1 cells with 20 μg/ml HTA 125 antibody significantly blocked silica-induced TNFα release by 27%. Furthermore, the TNFα content re-leased from cells expressing mutated TLR4 reduced by 30% in compared with that from the cells expressing wild type TLR4 after silica stimulation. Conclusion TLR4 mediates silica-induced TNFα release from macrophages.

Involvement of Toll-like receptor in silica-induced tumor necrosis factor a release from human macrophage cell line