PPAR Gamma agonists regulate tobacco smoke-induced toll like receptor 4 expression in alveolar macrophages

<jats:title>Abstract</jats:title> <jats:sec> <jats:title>Background</jats:title> <jats:p>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.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>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 <jats:italic>in vivo</jats:italic>. 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 12hrs, respectively pretreated with PBS, rosiglitazone (30 uM), rosiglitazone (30 uM) + BADGE (100 uM), 15d-PGJ2 (PPARγ agonist, 5 uM), 15d-PGJ2 (5 uM) + BADGE (100 uM), or BADGE (100 uM) alone for 30 min <jats:italic>in vitro</jats:italic>.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p> <jats:italic>In vivo,</jats:italic> rosiglitazone counteracted CS-induced LTB4 and IL-8 release and PPARγ downregulation, markedly lowering the expression of TLR4 and TLR2. <jats:italic>In vitro,</jats:italic> both rosiglitazone and 15d-PGJ2 inhibited CS-induced inflammation through the TLR4 signaling pathway.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>These results suggest that PPARγ agonists regulate inflammation in alveolar macrophages and may play a role in inflammatory diseases such as COPD.</jats:p> </jats:sec>