Increased expression of upstream TH2-cytokines in a mouse model of viral-induced asthma exacerbation

Persson, Irma Mahmutovic; Akbarshahi, Hamid; Menzel, Mandy; Brandelius, Angelica; Uller, Lena

doi:10.1186/s12967-016-0808-x

Cited by 28 publications

(39 citation statements)

References 47 publications

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“…Consistent with increased expression of TSLP, HDM stress could induce NF‐κB expression in airway epithelial cells from ITGB4 +/+ mice. These results were consistent with previous studies from different cells and animal models . In addition, a significantly increased expression of NF‐κB was detected in HDM stressed ITGB4 −/− mice group compared with HDM stressed ITGB4 +/+ group (Fig.…”

Section: Resultssupporting

confidence: 92%

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ITGB4is essential for containing HDM-induced airway inflammation and airway hyperresponsiveness

Liu

Lin

Zou

et al. 2018

Journal of Leukocyte Biology

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Airway epithelial cells play a significant role in the pathogenesis of asthma. Although the structural and functional defects of airway epithelial cells have been postulated to increase asthma susceptibility and exacerbate asthma severity, the mechanism and implication of these defects remain uncertain. Integrin β4 (ITGB4) is a structural adhesion molecule that is downregulated in the airway epithelium of asthma patients. In this study, we demonstrated that ITGB4 deficiency leads to severe allergy-induced airway inflammation and airway hyper-responsiveness (AHR) in mice. After house dust mite (HDM) challenge, epithelial cell-specific ITGB4-deleted mice showed increased lymphocyte, eosinophil, and neutrophil infiltration into lung compared with that of the wild-type mice. ITGB4 deficiency also resulted in increased expression of the Th2 cytokine IL-4, IL-13, and the Th17 cytokine IL-17A in the lung tissue and in the T cells after HDM challenge. The aggravated inflammation in ITGB4 defect mice was partly caused by enhanced disrupted epithelial barrier integrity after HDM stress, which induced the increased thymic stromal lymphopoietin secretion from airway epithelial cells. This study therefore demonstrates that ITGB4 plays a pivotal role in containing allergen-mediated lung inflammation and airway hyper-responsiveness in allergic asthma.

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Section: Resultssupporting

confidence: 92%

“…These results were consistent with previous studies from different cells and animal models. 42,43 In addition, a significantly increased expression of NF-B was detected in HDM stressed ITGB4 −/− mice group compared with HDM stressed ITGB4 +/+ group (Fig. 5B).…”

Section: Increased Expression Of Tslp Was Induced By Activation Of Nfmentioning

confidence: 85%

ITGB4is essential for containing HDM-induced airway inflammation and airway hyperresponsiveness

Liu

Lin

Zou

et al. 2018

Journal of Leukocyte Biology

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“…A meta‐phenome‐wide association study also revealed a novel association of an IFIH1 allele mutation to increased risk for asthma . In an experimental model, poly(I:C) and rhinovirus‐derived dsRNA exacerbated asthma . Taken together, RLRs play a nonredundant and critical role in the development and progression of asthma.…”

Section: Rig‐i‐like Receptorsmentioning

confidence: 93%

Innate immunity in allergy

Maeda

Caldez

Akira

2019

Allergy

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Innate immune system quickly responds to invasion of microbes and foreign substances through the extracellular and intracellular sensing receptors, which recognize distinctive molecular and structural patterns. The recognition of innate immune receptors leads to the induction of inflammatory and adaptive immune responses by activating downstream signaling pathways. Allergy is an immune‐related disease and results from a hypersensitive immune response to harmless substances in the environment. However, less is known about the activation of innate immunity during exposure to allergens. New insights into the innate immune system by sensors and their signaling cascades provide us with more important clues and a framework for understanding allergy disorders. In this review, we will focus on recent advances in the innate immune sensing system.

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“…Experiments were approved by the regional laboratory animal ethics committee in Malmö/Lund (permit no. M36-13) and performed as previously described [ 10 ]. In short, C57BL/6 wild-type and caspase-1 -/- mice (provided by Catharina Svanborg, Lund University, Lund, Sweden) were challenged with 25 µg house dust mite (HDM; Greer, Lenoir, NC, USA) 3 days·week −1 for 3 weeks and were subsequently exposed to three doses of 50 µg polyinosinic:polycytidylic acid (poly(I:C); InvivoGen, San Diego, CA, USA).…”

Section: Methodsmentioning

confidence: 99%

Caspase-1 deficiency reduces eosinophilia and interleukin-33 in an asthma exacerbation model

et al. 2017

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Rhinovirus infections are common triggers of asthma exacerbations. Viruses can activate the inflammasome, resulting in processing and activation of caspase-1. This recruitment triggers production of interleukin (IL)-1β and IL-18, which have been implicated in asthma. Elucidating the involvement of the inflammasome and its compartments, such as caspase-1, in asthma exacerbations is warranted.Gene expression of caspase-1 was measured in rhinovirus-infected primary bronchial epithelial cells of asthmatic and healthy donors 24 h post-infection. In an in vivo exacerbation experiment C57BL/6 wild-type and caspase-1-/- mice were challenged with house dust mite followed by exposures to the viral mimic poly(I:C). General lung inflammatory parameters and levels of T-helper type 2 (Th2)-upstream cytokines IL-33, thymic stromal lymphopoietin (TSLP) and IL-25 were assessed.Caspase-1 expression was elevated after rhinoviral infection exclusively in bronchial epithelial cells from asthmatics. In a translational mouse model of asthma exacerbation effects of caspase-1 on airway inflammation and Th2-upstream cytokines were explored. Caspase-1 deficient mice exhibited no alterations of general lung inflammatory parameters, but showed markedly reduced eosinophilia. Furthermore, the Th2-upstream cytokines IL-33, TSLP and IL-25 were reduced at exacerbation in mice lacking caspase-1.Rhinovirus infection increases bronchial epithelial caspase-1 in asthma. Caspase-1 may induce production of lung Th2-upstream cytokines and eosinophilia at exacerbations. Further targeting of caspase-1 signalling is warranted to explore its role in asthma exacerbations.

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Increased expression of upstream TH2-cytokines in a mouse model of viral-induced asthma exacerbation

Cited by 28 publications

References 47 publications

ITGB4is essential for containing HDM-induced airway inflammation and airway hyperresponsiveness

ITGB4is essential for containing HDM-induced airway inflammation and airway hyperresponsiveness

Innate immunity in allergy

Caspase-1 deficiency reduces eosinophilia and interleukin-33 in an asthma exacerbation model

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