Epithelial PI3K-δ Promotes House Dust Mite-Induced Allergic Asthma in NLRP3 Inflammasome-Dependent and -Independent Manners
10.4168/aair.2020.12.2.338
- Author:
So Ri KIM
1
;
Hae Jin PARK
;
Kyung Bae LEE
;
Hee Jung KIM
;
Jae Seok JEONG
;
Seong Ho CHO
;
Yong Chul LEE
Author Information
1. Division of Respiratory Medicine and Allergy, Department of Internal Medicine, Research Center for Pulmonary Disorders, Chonbuk National University Medical School, Jeonju, Korea. sori@jbnu.ac.kr, leeyc@jbnu.ac.kr
- Publication Type:Original Article
- Keywords:
Epithelial cell;
asthma;
house dust mite;
inflammasomes;
kinases
- MeSH:
Animals;
Asthma;
Cytokines;
Dust;
Epithelial Cells;
Epithelium;
Humans;
In Vitro Techniques;
Inflammasomes;
Inflammation;
Leukocytes;
Lung;
Mice;
Models, Animal;
Phosphotransferases;
Pyroglyphidae;
RNA, Small Interfering
- From:Allergy, Asthma & Immunology Research
2020;12(2):338-358
- CountryRepublic of Korea
- Language:English
-
Abstract:
PURPOSE: Phosphoinositide 3-kinase (PI3K)-δ-dependent Akt activation is known to play critical roles in various immune responses of white blood cells in which PI3K-δ isoform is mostly expressed in contrast to the classes IA PI3Ks p110α and p110β. However, the immunological role of PI3K-δ isoform is still controversial in airway epithelium under house dust mite (HDM)-induced allergic response. This study aimed to evaluate the role of PI3K-δ isoform in HDM-induced allergic responses, focusing on NLRP3 inflammasome activation in airway epithelium.METHODS: We used wild-type mice and PI3K-δ 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-δ activated HDM-induced NLRP3 inflammasome and epithelial cell-derived cytokines in the lung including airway epithelial cells. PI3K-δ KO mice or knock-down of PI3K-δ 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-δ isoform was observed in stimulated airway epithelial cells and the increases in epithelial cell-derived cytokines were markedly suppressed by blocking PI3K-δ, while these cytokine levels were independent of NLRP3 inflammasome activation.CONCLUSIONS: The results of this study suggest that PI3K-δ-isoform can promote HDM-induced allergic airway inflammation via NLRP3 inflammasome-dependent response as well as via NLRP3 inflammasome-independent epithelial cell activation.