Regulation of cigarette smoke-induced toll-like receptor 4 expression by peroxisome proliferator-activated receptor-gamma agonists in bronchial epithelial cells.

Background and objectiveThis study was designed to determine the effects of peroxisome proliferator-activated receptor-gamma (PPAR) on airway inflammatory response to cigarette smoke (CS) exposure. MethodsFor 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 PPAR agonist, rosiglitazone or a vehicle (saline). PPAR 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. PPAR 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 PPAR agonist rosiglitazone or 15-deoxy-(12,14)-PG J2 before CS exposure. BADGE was administered prior to the agonist treatment. PPAR, TLR4 and inhibitor of B (IB) expression levels were assessed by Western bot. ResultsCS exposure decreased PPAR expression, as well as increased IL-8, LTB4 and TLR4 expression levels in bronchial epithelial cells in vivo and in vitro. Moreover, PPAR 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-B). ConclusionCS exposure increased the pro-inflammatory activity of bronchial epithelial cells by affecting PPAR expression. Moreover, PPAR may play a significant role as a modulator of the TLR4-dependent inflammatory pathway through NF-B in bronchial epithelial cells. This study assessed the effect of PPAR on cigarette smoke-induced airway inflammation. PPAR contributes to the regulation of the TLR4-associated inflammation response to cigarette smoke via downregulation of NF-B in bronchial epithelial cells in vivo and in vitro.