Rosiglitazone, a peroxisome proliferator-activated receptor-gamma agonist, attenuates acrolein-induced airway mucus hypersecretion in rats.
BACKGROUND
Peroxisome proliferator-activated receptor-gamma (PPAR-gamma), a member of the ligand-activated nuclear receptor superfamily, has been shown to be implicated in anti-inflammatory and immunomodulatory responses, but its role in airway mucus hypersecretion remains not clear.


OBJECTIVE
To investigate the role of PPAR-gamma in airway mucus hypersecretion, we used an acrolein-exposed rat model treated with rosiglitazone, a peroxisome proliferator-activated receptor-gamma agonist.


METHODS
Rats were exposed to acrolein (3.0 ppm, 6h/day, 7 days/week) and orally administered with rosiglitazone (2, 4, 8 mg/kg) once daily for up to 2 weeks. The expressions of Muc5ac protein and mRNA, and infiltration of inflammatory cells and levels of inflammatory cytokines (interleukin (IL)-1beta, IL-8 and tumor necrosis factor (TNF)-alpha) in bronchoalveolar lavage fluid (BALF) were detected with real-time PCR, Western blot, cell counting and ELISA. In addition, the role of nuclear factor (NF)-kappaB pathway in this process was also explored.


RESULTS
Acrolein exposure significantly induced goblet cell hyperplasia in bronchial epithelium and Muc5ac mRNA and protein expressions in rat lungs, as well as the associated airway inflammation evidenced by the increased numbers of inflammatory cells and levels of inflammatory cytokines in BALF, which were attenuated with rosiglitazone treatment in a dose-dependent manner (P<0.05). Simultaneously, the increased expression of NF-kappaB and decreased expression of cytoplasmic IkappaB in acrolein-exposed lungs were reversed by rosiglitazone treatment.


CONCLUSIONS
These findings suggest that PPAR-gamma activation by its ligands can attenuate acrolein-induced airway mucus hypersecretion in rats, which may be involved in inhibition of NF-kappaB pathway.
Liu
Dai-Shun
DS
Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, Sichuan, PR China.
Liu
Wei-Jia
WJ
Chen
Lei
L
Ou
Xue-Mei
XM
Wang
Tao
T
Feng
Yu-Lin
YL
Zhang
Shang-Fu
SF
Xu
Dan
D
Chen
Ya-Juan
YJ
Wen
Fu-Qiang
FQ
D000171:Acrolein / Q000037:antagonists & inhibitors* / Q000276:immunology; D000818:Animals; D015153:Blotting, Western; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D004347:Drug Interactions; D020397:Goblet Cells / Q000187:drug effects / Q000276:immunology; D007150:Immunohistochemistry; D008171:Lung Diseases / Q000139:chemically induced* / Q000276:immunology; D008297:Male; D055271:Mucin 5AC / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology*; D016328:NF-kappa B / Q000276:immunology; D047495:PPAR gamma / Q000819:agonists* / Q000276:immunology; D012313:RNA / Q000737:chemistry / Q000235:genetics; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D020545:Respiratory Mucosa / Q000276:immunology* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*
D016207:Cytokines; D055271:Mucin 5AC; D016328:NF-kappa B; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D012313:RNA; D000171:Acrolein