Presentation: PI3K-Delta Isoform Aggravates Fungus-Induced Eosinophilic Allergic Airway Inflammation through the Induction of ER Stress ( World Allergy Congress)

Saturday, 17 October 2015

Hall D1 Foyer (Floor 3) (Coex Convention Center)

Yong Chul Lee, MD, PhD , Department of Internal Medicine, Chonbuk National University Medical School/Hospital, Jeonju, South Korea

So Ri Kim, MD, PhD , Department of Internal Medicine, Chonbuk National University Medical School/Hospital, Jeonju, South Korea

Kyung Bae Lee, MS , Department of Internal Medicine, Chonbuk National University Medical School/Hospital, Jeonju, South Korea

Soon Ha Kim, PhD , LG Life Sciences Ltd., Seoul, South Korea

Yang Keun Rhee, MD, PhD , Department of Internal Medicine, Chonbuk National University Medical School/Hospital, Jeonju, South Korea

Heung Bum Lee, MD, PhD , Department of Internal Medicine, Chonbuk National University Medical School/Hospital, Jeonju, South Korea

Seoung Ju Park, MD, PhD , Department of Internal Medicine, Chonbuk National University Medical School/Hospital, Jeonju, South Korea

Yeong Hun Choe Choe, MD, PhD , Department of Internal Medicine, Chonbuk National University Medical School/Hospital, Jeonju, South Korea

Seung Yong Park, MD, PhD , Department of Internal Medicine, Chonbuk National University Medical School/Hospital, Jeonju, South Korea

Jae Seok Jeong, MD , Chonbuk National University Medical School/Hospital, Jeonju, South Korea

Phosphoinositide 3-kinase (PI3K)-δ signaling and endoplasmic reticulum (ER) stress are critically involved in various inflammatory processes. However, there is no information concerning their interrelationship in allergic inflammation. In this study, we aimed to elucidate an association of ER stress with PI3K-δ signaling in fungus-induced allergic lung inflammation. Using Aspergillus fumigatus-exposed in vivo and in vitro experimental systems, we have investigated the role of PI3K-δ in the regulation of ER stress in the pathogenesis of allergic lung inflammation. The Aspergillus fumigatus-sensitized and -challenged mice showed that the expression of ER stress markers and the protein levels of unfolded protein response (UPR)-related markers in lung tissues were significantly increased after Aspergillus fumigatus challenge. Protein expression of ER stress markers was also remarkably elevated in Aspergillus fumigatus-stimulated cultured tracheal epithelial cells. However, administration of PI3K-δ inhibitor significantly reduced the increases in ER stress markers and UPR-related proteins in the lung. And, blockade of PI3K-δ signaling using PI3K-δ inhibitor or PI3K-δ specific siRNA also markedly reduced the expression of ER stress markers in Aspergillus fumigatus-stimulated cultured tracheal epithelial cells. Furthermore, inhibition of PI3K-δ or ER stress improved various pathophysiologic features in Aspergillus fumigatus-induced allergic lung inflammation. These findings suggest that PI3K-δ signaling is implicated in Aspergillus fumigatus-induced allergic lung inflammation through the modulation of ER stress.

4066 PI3K-Delta Isoform Aggravates Fungus-Induced Eosinophilic Allergic Airway Inflammation through the Induction of ER Stress