Activation of PI3K-d signaling pathway contributes to the generation of mitochondrial ROS and NLRP3 inflammasome in HDM-inhaled mice

In this study, we have investigated the effects of IC87114, a representative inhibitor of PI3K- isoform, on the HDM-induced airway inflammation and hyperresponsiveness. In addition, we tried to define the role of PI3K- in the HDM-induced NLRP3 inflammasome activation in airways using primary cultured tracheal epithelial cells.HDM-sensitized and -challenged mice showed the typical allergic airway inflammation and hyperresponsivenss, and the increased levels of Th2 cytokines, IL-17, IL-1β, and TNF-α in lungs. Moreover, we found the increases of mitochondrial ROS and the NLRP3 inflammasome activation in HDM-exposed lung. Very interestingly, the administration of IC87114 decreased the asthmatic features in HDM-sensitized and -challenged mice. Primary cultured tracheal epithelial cells from HDM-inhaled mice showed the increased expression of NLRP3 compared to the levels in cells from control mice. Pretreatment with IC87114 or transfection of siRNA for PI3K- dramatically reduced the expression of NLRP3 protein in primary cultured tracheal epithelial cells from HDM-inhaled mice. These findings suggest that PI3K- plays an important role in HDM-induced bronchial asthma through the regulation of NLRP3 activation mediated by mitochondrial ROS.
Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: 5.3 Allergy and Immunology Source Type: research