Allergy Asthma Immunol Res.  2020 Mar;12(2):338-358. 10.4168/aair.2020.12.2.338.

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

Affiliations
  • 1Division 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
  • 2Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Jeonju, Korea.
  • 3Division of Allergy and Immunology, Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.

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.

Keyword

Epithelial cell; asthma; house dust mite; inflammasomes; kinases
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