Epithelial PI3K-? Promotes House Dust Mite-Induced Allergic Asthma in NLRP3 Inflammasome-Dependent and -Independent Manners.

ABSTRACT: PURPOSE:Phosphoinositide 3-kinase (PI3K)-?-dependent Akt activation is known to play critical roles in various immune responses of white blood cells in which PI3K-? isoform is mostly expressed in contrast to the classes IA PI3Ks p110? and p110?. However, the immunological role of PI3K-? isoform is still controversial in airway epithelium under house dust mite (HDM)-induced allergic response. This study aimed to evaluate the role of PI3K-? isoform in HDM-induced allergic responses, focusing on NLRP3 inflammasome activation in airway epithelium. METHODS:We used wild-type mice and PI3K-? knock-out (KO) mice for HDM-induced asthma animal model and also performed in vitro experiments using primary cultured murine tracheal epithelial cells and human airway epithelial cells. RESULTS:PI3K-? activated HDM-induced NLRP3 inflammasome and epithelial cell-derived cytokines in the lung including airway epithelial cells. PI3K-? KO mice or knock-down of PI3K-? using siRNA exhibited the significant reduction in allergic asthmatic features and the suppression of NLRP3 inflammasome assembly as well as epithelial cell-derived cytokines. Interestingly, significantly increased expression of PI3K-? isoform was observed in stimulated airway epithelial cells and the increases in epithelial cell-derived cytokines were markedly suppressed by blocking PI3K-?, while these cytokine levels were independent of NLRP3 inflammasome activation. CONCLUSIONS:The results of this study suggest that PI3K-?-isoform can promote HDM-induced allergic airway inflammation via NLRP3 inflammasome-dependent response as well as via NLRP3 inflammasome-independent epithelial cell activation.

SUBMITTER: Kim SR 

PROVIDER: S-EPMC6997282 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature