Ciglitazone inhibits cigarette smoke solution-induced inflammatory responses in human middle ear epithelial cells

Objective: Peroxisome proliferator activated receptor-gamma (PPAR-gamma), a member of the nuclear hormone receptor superfamily, plays an important role in the regulation of mucosal inflammation. The aim of this study was to investigate the anti-inflammatory effect of a PPAR-gamma agonist, ciglitazone, on cigarette smoke solution (CSS)-induced inflammation in human middle ear epithelial cell lines (HMEECs). Design: HMEECs with or without ciglitazone pre-treatment were exposed to CSS in order to induce the inflammatory response. The suppressive effect of inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha) and cyclooxygenase-2(COX-2), were evaluated using real-time polymerase chain reaction and Western blotting. Results: Stimulation with CSS at 40 mu g/ml for 6 h resulted in a 4.1-fold increase in the expression of TNF-alpha mRNA in the HMEECs. CSS-induced up-regulation of TNF-alpha mRNA was decreased by more than 2.8-fold in cells pre-treated with ciglitazone. The up-regulation of COX-2 mRNA and increased COX-2 protein expression induced by CSS were also inhibited by more than 3.7-fold with ciglitazone pre-treatment. Conclusions: These findings suggest that the inflammatory response induced by CSS could be inhibited by ciglitazone, a PPAR-gamma agonist, in HMEECs. As such, PPAR-gamma agonists may have therapeutic potential for the treatment of otitis media. (C) 2012 Elsevier Ireland Ltd. All rights reserved.