NLRP3 inflammasome is activated via phosphoinositide 3-kinase {delta} pathway in Aspergillus fumigatus-induced allergic airway inflammation

In this study, we focused on an association of NLRP3 inflammasome activation with PI3K- signaling in Aspergillus fumigatus (Af)-induced allergic lung inflammation. Using Af-exposed in vivo and in vitro experimental systems, we have investigated the role of PI3K- 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-1bin lungs was significantly increased after the challenge in Af-sensitized and -challenged mice. Protein expression of NLRP3 and caspase-1 was also remarkably elevated in Af-stimulated cultured tracheal epithelial cells. But, administration of PI3K- inhibitor significantly reduced the increases of the protein levels of NLRP3, caspase-1, and IL-1b in the lung. And, blockade of PI3K- signaling using PI3K- inhibitor or PI3K- specific siRNA also markedly reduced increased protein expression of NLRP3 and caspase-1 in Af-stimulated cultured tracheal epithelial cells. Furthermore, inhibition of PI3K- improved various pathophysiologic features in Af-induced allergic lung inflammation. Lastly, neutralization of IL-1b substantially reduced airway inflammation and hyperresponsiveness in The Af-sensitized and -challenged mice.These findings suggest that PI3K- signaling influences Af-induced allergic lung inflammation via the regulation of NLRP3 inflammasome activation.
Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: 5.3 Allergy and Immunology Source Type: research