Dataset Information

Phosphoinositide 3-kinase-? regulates fungus-induced allergic lung inflammation through endoplasmic reticulum stress.

ABSTRACT:

Background

Sensitisation with Aspergillus fumigatus (Af) is known to be associated with severe allergic lung inflammation, but the mechanism remains to be clarified. Phosphoinositide 3-kinase (PI3K)-? and endoplasmic reticulum (ER) stress are suggested to be involved in steroid-resistant lung inflammation. We aimed to elucidate the role of PI3K-? and its relationship with ER stress in fungus-induced allergic lung inflammation.

Methods

Using Af-exposed in vivo and in vitro experimental systems, we examined whether PI3K-? regulates ER stress, thereby contributing to steroid resistance in fungus-induced allergic lung inflammation. Moreover, we checked expression of an ER stress marker in lung tissues isolated from patients with allergic bronchopulmonary aspergillosis.

Results

Af-exposed mice showed that ER stress markers, unfolded protein response (UPR)-related proteins, phosphorylated Akt, generation of mitochondrial reactive oxygen species (mtROS), eosinophilic allergic inflammation, and airway hyperresponsiveness (AHR) were increased in the lung. Similarly, glucose-regulated protein 78 was increased in lung tissues of patients with ABPA. A PI3K-? inhibitor reduced Af-induced increases in ER stress markers, UPR-related proteins, allergic inflammation and AHR in mice. However, dexamethasone failed to reduce Af-induced allergic inflammation, AHR and elevation of ER stress. Administration of an ER stress inhibitor or a mtROS scavenger improved Af-induced allergic inflammation. The PI3K-? inhibitor reduced Af-induced mtROS generation and the mtROS scavenger ameliorated ER stress. In primary cultured tracheal epithelial cells, Af-induced ER stress was inhibited by blockade of PI3K-?.

Conclusions

These findings suggest that PI3K-? regulates Af-induced steroid-resistant eosinophilic allergic lung inflammation through ER stress.

SUBMITTER: Lee KS

PROVIDER: S-EPMC4717427 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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Publications

Phosphoinositide 3-kinase-δ regulates fungus-induced allergic lung inflammation through endoplasmic reticulum stress.

Lee Kyung Sun KS Jeong Jae Seok JS Kim So Ri SR Cho Seong Ho SH Kolliputi Narasaiah N Ko Yun Hee YH Lee Kyung Bae KB Park Suk Chul SC Park Hae Jin HJ Lee Yong Chul YC

Thorax 20151105 1

<h4>Background</h4>Sensitisation with Aspergillus fumigatus (Af) is known to be associated with severe allergic lung inflammation, but the mechanism remains to be clarified. Phosphoinositide 3-kinase (PI3K)-δ and endoplasmic reticulum (ER) stress are suggested to be involved in steroid-resistant lung inflammation. We aimed to elucidate the role of PI3K-δ and its relationship with ER stress in fungus-induced allergic lung inflammation.<h4>Methods</h4>Using Af-exposed in vivo and in vitro experime ...[more]

PMID: 26543090

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