title: Regulation of cigarette smoke-induced toll-like receptor 4 expression by peroxisome proliferator-activated receptor-gamma agonists in bronchial epithelial cells.
abstract: OBJECTIVE
  This study was designed to determine the effects of peroxisome proliferator-activated receptor-gamma (PPARγ) on airway inflammatory response to cigarette smoke (CS) exposure.
  
  
  METHODS
  For the in vivo experiments, 50 male Wistar rats were randomly assigned to one of four groups and were exposed to CS and pretreatment with a PPARγ agonist, rosiglitazone or a vehicle (saline). PPARγ antagonist bisphenol A diglycidyl ether (BADGE) or saline was administered before rosiglitazone treatment. Leukotriene B4 (LTB4) and interleukin-8 (IL-8) were measured by enzyme-linked immunosorbent assay. PPARγ and toll-like receptor 4 (TLR4) expression levels were assessed by immunohistochemistry and real-time polymerase chain reaction. For the in vitro experiments, human bronchial epithelial cells were stimulated with CS or phosphate buffer saline, pretreated with PPARγ agonist rosiglitazone or 15-deoxy-(Δ12,14)-PG J2 before CS exposure. BADGE was administered prior to the agonist treatment. PPARγ, TLR4 and inhibitor of κB (IκBα) expression levels were assessed by Western bot.
  
  
  RESULTS
  CS exposure decreased PPARγ expression, as well as increased IL-8, LTB4 and TLR4 expression levels in bronchial epithelial cells in vivo and in vitro. Moreover, PPARγ ligands counteracted CS-induced airway inflammation by reducing IL-8 and LTB4 expression levels that are associated with TLR4 and nuclear factor-kappa B (NF-κB).
  
  
  CONCLUSIONS
  CS exposure increased the pro-inflammatory activity of bronchial epithelial cells by affecting PPARγ expression. Moreover, PPARγ may play a significant role as a modulator of the TLR4-dependent inflammatory pathway through NF-κB in bronchial epithelial cells.
authors.affiliation: Institute of Respiratory Disease, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yin
authors.forename: Gang
authors.initials: G
authors.lastname: Hou
authors.forename: Er-ran
authors.initials: ER
authors.lastname: Li
authors.forename: Qiu-yue
authors.initials: QY
authors.lastname: Wang
authors.forename: Jian
authors.initials: J
authors.lastname: Kang
mesh_terms: D000818:Animals; D001559:Benzhydryl Compounds / Q000494:pharmacology; D001980:Bronchi / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D004852:Epoxy Compounds / Q000494:pharmacology; D066298:In Vitro Techniques; D016209:Interleukin-8 / Q000378:metabolism; D007975:Leukotriene B4 / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D047495:PPAR gamma / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000378:metabolism; D011014:Pneumonia / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D000077154:Rosiglitazone; D012907:Smoking / Q000009:adverse effects*; D045162:Thiazolidinediones / Q000494:pharmacology*; D051197:Toll-Like Receptor 4 / Q000187:drug effects* / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D004852:Epoxy Compounds; D016209:Interleukin-8; D007975:Leukotriene B4; D016328:NF-kappa B; D047495:PPAR gamma; D000077154:Rosiglitazone; D045162:Thiazolidinediones; D051197:Toll-Like Receptor 4; C495347:Tlr4 protein, rat; C019273:bisphenol A diglycidyl ether; D000098826:Bisphenol A Compounds
keywords: bronchial epithelial cell; cigarette smoke; nuclear factor-kappa B; peroxisome proliferator-activated receptor γ; toll-like receptor 4