Abstract:

Objective To investigate the inhibiting effect of Fosinoprilat (Fos) on expression of Toll-like receptor 4 (TLR4）in lipopolysaccharide (LPS) activated human leucocythemia monocytic series cells (THP1). Methods THP1 cells were cultured, and the concentration was adjusted to 1×106/mL. Eight groups were divided: control group (normal THP1 cells), LPS stimulation group (THP1 cells+LPS), DMSO group (THP1 cells+LPS+DMSO) and Fos intervention groups (THP1 cells+LPS+Fos, with Fos concentrations of 10,5,1,0.5,0.25 μmol/L, respectively). Real-time PCR was employed to detect the expression of TLR4 mRNA in THP1 cells, Western blotting was used to detected the expression of TLR4 and NF-κB protein, and the expression of TLR4 protein was detected by flow cytometry. Results The expression of TLR4 mRNA and protein of THP1 cells in LPS stimulation group was significantly higher than that in control group (P<0.05). The expression of TLR4 mRNA and protein of THP1 cells in Fos intervention groups (especially for 1 μmol/L Fos and 0.5 μmol/L Fos) was lower than that in LPS stimulation group. The expression of NF-κB protein in LPS stimulation group was significantly higher than that in Fos intervention groups (P<0.05). Conclusion Fos can downregulate the expression of TLR4 and inhibit the activity of NF-κB in LPS activated THP1 cells.

Key words: Toll-like receptor 4, Fosinoprilat, lipopolysaccharide, leucocythemia monocytic series