interleukin-8 and 2-2-bis(4-glycidyloxyphenyl)propane

This study was designed to determine the effects of peroxisome proliferator-activated receptor-gamma (PPARγ) on airway inflammatory response to cigarette smoke (CS) exposure.. 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.. 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).. 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.

Topics: Animals; Benzhydryl Compounds; Bronchi; Cell Survival; Cells, Cultured; Disease Models, Animal; Down-Regulation; Epithelial Cells; Epoxy Compounds; In Vitro Techniques; Interleukin-8; Leukotriene B4; Male; NF-kappa B; Pneumonia; PPAR gamma; Rats; Rats, Wistar; Rosiglitazone; Smoking; Thiazolidinediones; Toll-Like Receptor 4; Up-Regulation