福辛普利通过抑制单核细胞 TLR4/NF-κB 信号通路缓解脂多糖（LPS）诱导的炎症。

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

机构信息

Department of Cardiology, Central Hospital, Fengxian District, Shanghai 201400, China.

出版信息

Cell Immunol. 2013 Jul-Aug;284(1-2):182-6. doi: 10.1016/j.cellimm.2013.06.009. Epub 2013 Jun 28.

DOI:10.1016/j.cellimm.2013.06.009

PMID:24036412

Abstract

OBJECTIVE

To evaluate the effect of the fosinoprilat on lipopolysacharides (LPS) induced inflammation in monocytes in vitro.

METHODS

Human mononuclear THP1 cells were cultured in complete medium, treated with or without LPS and different concentrations (0,0.25,0.5,1,5,and 10μmol/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).

RESULTS

Both the 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.

CONCLUSION

The inhibitory effect of the fosinoprilat on the TRL4/NF-κB signaling pathway reveals a potential anti-inflammatory and anti-atherosclerosis target.

摘要

目的

评估福辛普利拉对体外单核细胞脂多糖（LPS）诱导炎症的影响。

方法

人单核细胞 THP1 细胞在完全培养基中培养，用或不用 LPS 和不同浓度（0、0.25、0.5、1、5 和 10μmol/L）的福辛普利拉处理。通过实时 RT-PCR 检测 Toll 样受体（TLR4）mRNA 表达，通过流式细胞术检测单核细胞表面 TLR4 蛋白水平。通过 Western blot 检测核因子-κB（NF-κB）蛋白水平。通过 ELISA 分析不同组的 THP1 细胞培养上清液，以检测白细胞介素（IL）-1β、IL-6 和肿瘤坏死因子（TNF-α）的水平。