Thursday, 15 October 2015: 16:15 - 16:30
Room R2 ABC (Floor 3) (Coex Convention Center)
NLRP3 inflammasome is activated by various pathophysiological stimuli and plays a cruicial role in th pathogenesis of several pulmonary disorders. Phosphoinositide 3-kinase delta (PI3K-δ) signaling has been repoted to be implicated in the pathogenesis of allergic airway inflammation. However, it is still not known about the role of PI3K-δ in relation to activation of the NLRP3 inflammasome in airway inflammation. In this study, we focused on an association of NLRP3 inflammasome activation with PI3K-δ signaling in Aspergillus fumigatus-induced allergic lung inflammation. Using Aspergillus fumigatus-exposed in vivo and in vitro experimental systems, we have investigated the role of PI3K-δ in the regulation of NLRP3 inflammasome activation in the pathogenesis of fungus-induced allergic lung inflammation. The protein expression of NLRP3, caspase-1, and IL-1β in lungs was significantly increased after Aspergillus fumigatus challenge in Aspergillus fumigatus-sensitized and -challenged mice. Protein expression of NLRP3 and caspase-1 was also remarkably elevated in Aspergillus fumigatus-stimulated cultured tracheal epithelial cells. But, administration of PI3K-δ inhibitor significantly reduced the increases of the protein levels of NLRP3, caspase-1, and IL-1β in the lung. And, blockade of PI3K-δ signaling using PI3K-δ inhibitor or PI3K-δ specific siRNA also markedly reduced increased protein expression of NLRP3 and caspase-1 in Aspergillus fumigatus-stimulated cultured tracheal epithelial cells. Furthermore, inhibition of PI3K-δ improved various pathophysiologic features in Aspergillus fumigatus-induced allergic lung inflammation. Lastly, neutralization of IL-1β substantially reduced airway inflammation and hyperresponsiveness in The Aspergillus fumigatus-sensitized and -challenged mice. These findings suggest that PI3K-δ signaling influences Aspergillus fumigatus-induced allergic lung inflammation via the regulation of NLRP3 inflammasome activation.