title: Fosinoprilat alleviates lipopolysaccharide (LPS)-induced inflammation by inhibiting TLR4/NF-κB signaling in monocytes.
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.
  
  
  CONCLUSIONS
  The inhibitory effect of the fosinoprilat on the TRL4/NF-κB signaling pathway reveals a potential anti-inflammatory and anti-atherosclerosis target.
authors.affiliation: Department of Cardiology, Central Hospital, Fengxian District, Shanghai 201400, China. Electronic address: yangss@medmail.com.cn.
authors.forename: Shuansuo
authors.initials: S
authors.lastname: Yang
authors.forename: Ruogu
authors.initials: R
authors.lastname: Li
authors.forename: Xinkai
authors.initials: X
authors.lastname: Qu
authors.forename: Lei
authors.initials: L
authors.lastname: Tang
authors.forename: Guanghao
authors.initials: G
authors.lastname: Ge
authors.forename: Weiyi
authors.initials: W
authors.lastname: Fang
authors.forename: Zengyong
authors.initials: Z
authors.lastname: Qiao
authors.forename: Jiangwei
authors.initials: J
authors.lastname: Ma
authors.forename: Yuemei
authors.initials: Y
authors.lastname: Hou
authors.forename: Huajin
authors.initials: H
authors.lastname: Liu
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D015153:Blotting, Western; D002460:Cell Line; D005434:Flow Cytometry; D017328:Fosinopril / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D053583:Interleukin-1beta / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D009000:Monocytes; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D053583:Interleukin-1beta; D015850:Interleukin-6; D016328:NF-kappa B; D012333:RNA, Messenger; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D017328:Fosinopril; C046965:fosinoprilat
keywords: Anti-atherosclerosis; Fosinoprilat; Lipopolysacharides; Toll-like receptors