title: PPARγ agonists regulate tobacco smoke-induced Toll like receptor 4 expression in alveolar macrophages.
abstract: BACKGROUND
  Peroxisome proliferator-activated receptor-gamma (PPARγ) is a ligand-activated transcription factor that exerts multiple biological effects. Growing evidence suggests that PPARγ plays an important role in inflammation; however, the effects of this transcription factor on the inflammation caused by smoking are unclear.
  
  
  METHODS
  We measured the expression of inflammatory cytokines (leukotriene B4, LTB4 and interleukin 8, IL-8), PPARγ and toll-like receptors (TLR2 and TLR4) in alveolar macrophages (AMs) harvested from rats exposed to cigarette smoke (CS) for 3 months in vivo. Some of the rats were pre-treated with rosiglitazone (PPARγ agonist, 3 mg/kg/day, ip), rosiglitazone (3 mg/kg/day, ip) + BADGE (bisphenol A diglycidyl ether, a PPARγ antagonist, 30 mg/kg/day, ig), or BADGE alone (30 mg/kg/day, ig). We also measured the expression of PPARγ, TLR2, TLR4 and nuclear factor-kappaB (NF-κB) in AMs gained from normal rats, which exposed to 5% CSE (cigarette smoke extract) for 12 hrs, respectively pretreated with PBS, rosiglitazone (30 uM), rosiglitazone (30 uM) + BADGE (100 uM), 15 d-PGJ2 (PPARγ agonist, 5 uM), 15 d-PGJ2 (5 uM) + BADGE (100 uM), or BADGE (100 uM) alone for 30 min in vitro.
  
  
  RESULTS
  In vivo, rosiglitazone counteracted CS-induced LTB4 and IL-8 release and PPARγ downregulation, markedly lowering the expression of TLR4 and TLR2. In vitro, both rosiglitazone and 15 d-PGJ2 inhibited CS-induced inflammation through the TLR4 signaling pathway.
  
  
  CONCLUSIONS
  These results suggest that PPARγ agonists regulate inflammation in alveolar macrophages and may play a role in inflammatory diseases such as COPD.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yin
authors.forename: Gang
authors.initials: G
authors.lastname: Hou
authors.forename: Erran
authors.initials: E
authors.lastname: Li
authors.affiliation: Institute of Respiratory Disease, The First Affiliated Hospital of China Medical University, Shen Yang City, China. qywang2002@hotmail.com.
authors.forename: Qiuyue
authors.initials: Q
authors.lastname: Wang
authors.forename: Jian
authors.initials: J
authors.lastname: Kang
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D015536:Down-Regulation / Q000235:genetics; D019570:Inhalation Exposure / Q000009:adverse effects*; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008297:Male; D047495:PPAR gamma / Q000819:agonists* / Q000378:metabolism*; D010587:Phagocytosis / Q000187:drug effects / Q000502:physiology; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D000077154:Rosiglitazone; D012907:Smoking / Q000009:adverse effects / Q000378:metabolism* / Q000473:pathology; D045162:Thiazolidinediones / Q000494:pharmacology; D051197:Toll-Like Receptor 4 / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D047495:PPAR gamma; D045162:Thiazolidinediones; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; D000077154:Rosiglitazone