Fosinoprilat alleviates lipopolysaccharide (LPS)-induced inflammation by inhibiting TLR4/NF-κB signaling in monocytes

AbstractObjective luate the effect of the fosinoprilat on lipopolysacharides (LPS) induced inflammation in monocytes in vitro. s mononuclear THP1 cells were cultured in complete medium, treated with or without LPS and different concentrations (0, 0.25, 0.5, 1, 5, and 10 μmol/L) of fosinoprilat. Toll-like receptor (TLR4) mRNA expression was detected by real-time RT-PCR and TLR4 protein level on the surface of monocyte was determined by flow cytometry. Nuclear factor-kappa B (NF-κB) protein level was detected by Western blotting. Cultured supernatant of the THP1 cells in different groups were analyzed by ELISA to detect the levels of interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF-α). s he mRNA and surface protein level of the TLR4 in the THP1 cells were enhanced by the LPS treatment and down-regulated by pretreatment of the fosinoprilat. Accordingly, LPS-induced NF-κB protein was decreased by the fosinoprilat treatment. The increasing secretion of IL-1β, IL-6 and TNF-α induced by LPS could also be attenuated by the fosinoprilat treatment. sion hibitory effect of the fosinoprilat on the TRL4/NF-κB signaling pathway reveals a potential anti-inflammatory and anti-atherosclerosis target.