Effect Of PPARγ And Its Ligand On Airway Mucus Hypersecretion In Rats And Its Molecular Mechanisms

Objective To explore the molecular mechanisms in airway mucushypersecretion induced by acrolein. To examine the effect of peroxisomeproliferators activated receptor gamma and its ligand on airway mucushypersecretion and to investigate its molecular mechanism in airway mucushypersecretion.Methods The rat airway mucus hypersecretion was induced by aerosolacrolein inhalation. Rats were exposed to acrolein alone (acrolein 3.0μg/ml, 6h/day, together12 days), or simultaneously orally treated withrosiglitazone 2mg/kg,4mg/kg or 8mg/kg. Histopathology examination lungtissue section stained with H&E and AB-PAS. The levels of IL-1β, IL-8and TNF-αin BALF were assayed with ELISA. Muc5ac, PPARγ, NF-κB and I-κB in bronchial epithelia were detected by real time RT-PCR orimmunohistochemistry. The protein levels of NF-κB and I-κB weredetected by Western blot.Results Acrolein significantly induced the expression of Muc5ac mRNA and protein in rat bronchial epithelia, and increased the levels of IL-1β, IL-8and TNF-αin BALF. Acrolein increased the staining of NF-κB incytoplasm and the ratio of nuclear transposition in airway epithelial cells.Moreover, acrolein decreased the expression of I-κB in airway epithelialcells. The expression of Muc5ac mRNA was positively correlated with NF-κB activation, the levels of IL-1β, IL-8 and TNF-α. Rosiglitazoneupregulated the expressions of PPARγmRNA and PPARγprotein,reduced the expression of Muc5ac, downregulated the levels of IL-1β, IL-8and TNF-αin a concentration-dependent pattern. Moreove, rosiglitazoneinhibited the activation of NF-κB and decomposition of I-κB. Theexpression of PPARγin airway was negatively correlated with NF-κBactivation, the expression of Muc5ac mRNA, the levels of IL-1β, IL-8 andTNF-α.Conclusion The activation of NF-κB was involved in airwayinflammation and airway mucus hypersecretion induced by acrolein; PPARγand its ligand inhibits airway inflammation and airway mucushypersecretion induced by acrolein. The inhibitory effect of PPARγand itsligand on airway mucus hypersecretion may be through the reduction of NF-κB activation and inflammatory cytokines released.