Dataset Information

Allergy immunotherapy restores airway epithelial barrier dysfunction through suppressing IL-25 -induced endoplasmic reticulum stress in asthma.

ABSTRACT: Constant exposure to allergen triggers destructive type 2 cell-mediated inflammation. The effect of allergen specific immunotherapy (SIT) in maintaining airway epithelial barrier function in asthma remains unknown. In the current study, we showed that SIT maintained airway epithelial homeostasis in mice exposed to dermatophagoides farinae (Der f), which induced increased expression of IL-25, endoplasmic reticulum (ER) stress and airway epithelial apoptosis. Meanwhile, SIT treatment ameliorated airway inflammatory infiltration and hyper-responsiveness in allergic mice. SIT treatment restored the airway epithelial integrity, attenuated Der f -induced airway epithelial ER stress and epithelial apoptosis. We also found that 4-PBA, an inhibitor of ER stress, suppressed airway epithelial ER stress and apoptosis in vitro. The pathological changes were partially induced by IL-25-induced ER stress, epithelial tight junction damage, and cell apoptosis in airways following allergen exposure. Furthermore, IL-25 induced ER stress in airway epithelial cells in vitro. The IL-25-induced airway epithelial apoptosis dependent on PERK activity was inhibited by 4-PBA. Taken together, we demonstrate that SIT is effective in allergic asthma and dependent on its depressive effect on the expression of IL-25, epithelial integrity damage, and epithelial ER stress.

SUBMITTER: Yuan X

PROVIDER: S-EPMC5962552 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Allergy immunotherapy restores airway epithelial barrier dysfunction through suppressing IL-25 -induced endoplasmic reticulum stress in asthma.

Yuan Xiefang X Wang Junyi J Li Yin Y He Xiang X Niu Bin B Wu Dehong D Lan Nan N Wang Xiaoyun X Zhang Yun Y Dai Xi X Wang Xing X Liu Zhigang Z Li Guoping G

Scientific reports 20180521 1

Constant exposure to allergen triggers destructive type 2 cell-mediated inflammation. The effect of allergen specific immunotherapy (SIT) in maintaining airway epithelial barrier function in asthma remains unknown. In the current study, we showed that SIT maintained airway epithelial homeostasis in mice exposed to dermatophagoides farinae (Der f), which induced increased expression of IL-25, endoplasmic reticulum (ER) stress and airway epithelial apoptosis. Meanwhile, SIT treatment ameliorated a ...[more]

PMID: 29784924

Similar Datasets

Project description:BackgroundSevere asthma is associated with substantial mortality and has unmet therapeutic need. A subset of severe asthma is characterized by neutrophilic airway inflammation. Classically activated (or M1) macrophages which express IL-12 and IL-23 are associated with airway neutrophilia in asthma. Exogenous IL-25 was reported to suppress intestinal inflammation in animal models of inflammatory bowel diseases via suppressing IL-12 and IL-23 production. We hypothesize that IL-25 ameliorates airway neutrophilia via inhibiting macrophage M1 polarization and the expression of IL-12 and IL-23 in asthma.MethodsIn a mouse model of neutrophil-dominant allergic airway inflammation, the effect of mouse recombinant IL-25 on airway inflammation were assessed by H&E staining and bronchoalveolar lavage (BAL) cell counting. The percentage of M1 macrophages in lung tissue and BAL cells were analyzed by flow cytometry. Quantitative PCR and immunostaining were performed to measure the expression of Il12, Il23, and inflammatory cytokines. Mechanistic experiments were performed in primary culture of macrophages from mouse lungs. The expression of IL-12, IL-23 and IL-25 in sputum was analyzed in a cohort of severe asthma and subjects with eosinophilic or non-eosinophilic asthma.ResultsIntranasal administration of IL-25 markedly decreased the number of neutrophils in BAL cells in a murine model of neutrophil-dominant allergic airway inflammation. Moreover, exogenous IL-25 decreased the number of M1 macrophages, and reduced the expression of IL-12, IL-23 in the lungs of the mouse model. Exogenous IL-25 also inhibited the expression of inflammatory cytokines IL-1β, IFN-γ, TNF-α and IL-17 A. In vitro, IL-25 suppressed IL-12 and IL-23 expression in lipopolysaccharide (LPS)-stimulated primary culture of mouse pulmonary macrophages. Mechanistically, IL-25 inhibited LPS-induced c-Rel translocation to nucleus via STAT3-dependent signaling. In a cohort of severe asthma, IL-25 protein levels in sputum were significantly lower than control subjects. The transcript levels of IL-12 and IL-23 were increased whereas IL-25 transcripts were decreased in sputum cells from subjects with non-eosinophilic asthma compared to eosinophilic asthma.ConclusionsIL-25 expression is downregulated in subjects with severe or non-eosinophilic asthma. Exogenous IL-25 ameliorates airway neutrophilia, at least in part, via inhibiting macrophage M1 polarization and the expression of IL-12 and IL-23.

Dataset Information

Allergy immunotherapy restores airway epithelial barrier dysfunction through suppressing IL-25 -induced endoplasmic reticulum stress in asthma.

Publications

Allergy immunotherapy restores airway epithelial barrier dysfunction through suppressing IL-25 -induced endoplasmic reticulum stress in asthma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets