PPAR? agonists regulate tobacco smoke-induced Toll like receptor 4 expression in alveolar macrophages.

ABSTRACT:

Background

Peroxisome proliferator-activated receptor-gamma (PPAR?) is a ligand-activated transcription factor that exerts multiple biological effects. Growing evidence suggests that PPAR? plays an important role in inflammation; however, the effects of this transcription factor on the inflammation caused by smoking are unclear.

Methods

We measured the expression of inflammatory cytokines (leukotriene B4, LTB4 and interleukin 8, IL-8), PPAR? and toll-like receptors (TLR2 and TLR4) in alveolar macrophages (AMs) harvested from rats exposed to cigarette smoke (CS) for 3 months in vivo. Some of the rats were pre-treated with rosiglitazone (PPAR? agonist, 3 mg/kg/day, ip), rosiglitazone (3 mg/kg/day, ip)?+ BADGE (bisphenol A diglycidyl ether, a PPAR? antagonist, 30 mg/kg/day, ig), or BADGE alone (30 mg/kg/day, ig). We also measured the expression of PPAR?, TLR2, TLR4 and nuclear factor-kappaB (NF-?B) in AMs gained from normal rats, which exposed to 5% CSE (cigarette smoke extract) for 12 hrs, respectively pretreated with PBS, rosiglitazone (30 uM), rosiglitazone (30 uM)?+?BADGE (100 uM), 15 d-PGJ2 (PPAR? agonist, 5 uM), 15 d-PGJ2 (5 uM)?+?BADGE (100 uM), or BADGE (100 uM) alone for 30 min in vitro.

Results

In vivo, rosiglitazone counteracted CS-induced LTB4 and IL-8 release and PPAR? downregulation, markedly lowering the expression of TLR4 and TLR2. In vitro, both rosiglitazone and 15 d-PGJ2 inhibited CS-induced inflammation through the TLR4 signaling pathway.

Conclusions

These results suggest that PPAR? agonists regulate inflammation in alveolar macrophages and may play a role in inflammatory diseases such as COPD.

SUBMITTER: Yin Y 

PROVIDER: S-EPMC4007599 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature