Leukotriene receptor antagonist attenuated airway inflammation and hyperresponsiveness in a double-stranded RNA-induced asthma exacerbation model

Ujino, Mariko; Sugimoto, Naoya; Koizumi, Yuta; Ro, Shoki; Kojima, Yasuhiro; Kamiyama-Hara, Asae; Yamashita, Naomi; Ohta, Ken; Nagase, Hiroyuki

doi:10.1016/j.alit.2017.05.004

Cited by 9 publications

(6 citation statements)

References 34 publications

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“…Virusderived dsRNA induces inflammatory cytokine production in the respiratory tract of asthma patients and eosinophils and neutrophils accumulate in the respiratory tract, causing asthma exacerbation [40]. Several studies have used antigen (HDM or OVA) and poly(I:C) in virus-induced asthma exacerbation models in mice [41][42][43][44]. The present study therefore examined HDM and poly(I:C) administrations to mimic virus-induced asthma exacerbation.…”

Section: Discussionmentioning

confidence: 99%

The non-antibiotic macrolide EM900 attenuates HDM and poly(I:C)-induced airway inflammation with inhibition of macrophages in a mouse model

et al. 2019

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Objective Macrolides have been reported to reduce the exacerbation of severe asthma. The aim of this study was to clarify the effects and mechanisms of EM900, a non-antibiotic macrolide, on allergic airway inflammation. Methods Mice were sensitized and challenged by house dust mite (HDM), then exposed to polyinosinic-polycytidylic acid (poly(I:C)) as a model of asthma complicated with viral infection. Mice were administered with EM900. Airway inflammation was assessed from inflammatory cells in bronchoalveolar lavage fluid (BALF) and cytokines in lung tissues. Lung interstitial macrophages were counted by flow cytometry. Cytokine production, phosphorylation of NF-κB, and p38 in macrophages were examined by ELISA and western blotting. Results Counts of cells in BALF and concentrations of IL-13, IL-5, RANTES, IL-17A, and MIP-2 were significantly decreased by EM900 compared to those without EM900. Percentages of lung interstitial macrophages were significantly decreased with EM900. Concentrations of IL-6, RANTES, and MIP-2 induced by HDM and poly(I:C) were significantly suppressed by EM900 through the suppression of NF-κB and p38 phosphorylation in macrophages. Conclusions HDM and poly(I:C)-induced airway inflammation is attenuated by EM900 with the inhibition of lung interstitial macrophages. Clinical use of EM900 is expected, because EM900 has inhibitory effects against airway inflammation without inducing bacterial drug resistance.

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Section: Discussionmentioning

confidence: 99%

The non-antibiotic macrolide EM900 attenuates HDM and poly(I:C)-induced airway inflammation with inhibition of macrophages in a mouse model

et al. 2019

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“…Both CysLT 1 antagonists are administered orally and are preferred by children over inhaled corticosteroids [ 71 ]. Recently, montelukast additionally exhibited potential to reduce airway inflammation and hyperresponsiveness in a viral-triggered asthma exacerbation model [ 178 ].…”

Section: Eicosanoids and Eosinophilsmentioning

confidence: 99%

Emerging Role of Phospholipase-Derived Cleavage Products in Regulating Eosinophil Activity: Focus on Lysophospholipids, Polyunsaturated Fatty Acids and Eicosanoids

Knuplez

Sturm

Marsche

2021

IJMS

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Eosinophils are important effector cells involved in allergic inflammation. When stimulated, eosinophils release a variety of mediators initiating, propagating, and maintaining local inflammation. Both, the activity and concentration of secreted and cytosolic phospholipases (PLAs) are increased in allergic inflammation, promoting the cleavage of phospholipids and thus the production of reactive lipid mediators. Eosinophils express high levels of secreted phospholipase A2 compared to other leukocytes, indicating their direct involvement in the production of lipid mediators during allergic inflammation. On the other side, eosinophils have also been recognized as crucial mediators with regulatory and homeostatic roles in local immunity and repair. Thus, targeting the complex network of lipid mediators offer a unique opportunity to target the over-activation and ‘pro-inflammatory’ phenotype of eosinophils without compromising the survival and functions of tissue-resident and homeostatic eosinophils. Here we provide a comprehensive overview of the critical role of phospholipase-derived lipid mediators in modulating eosinophil activity in health and disease. We focus on lysophospholipids, polyunsaturated fatty acids, and eicosanoids with exciting new perspectives for future drug development.

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“…Of particular further interest are the recent reports that the leukotriene receptor antagonist montelukast not only suppresses inflammation in a poly I:C‐induced asthma exacerbation model in mice, but also suppresses LPS‐induced MMP‐13 expression in mouse osteoblasts . However, the effects of montelukast on bronchial epithelial repair in our model remain to be investigated.…”

Section: Discussionmentioning

confidence: 97%

Targeting matrix metalloproteinase‐13 in bronchial epithelial repair

Howell

Smith

Shute

2018

Clin Experimental Allergy

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Bronchial epithelial repair is limited by endothelin and by MMP-13, a protease that degrades coagulation factors, such as fibrinogen, and matrix proteins essential for epithelial repair. Further studies with primary cells from patients are needed to confirm whether repurposing bosentan and inhibitors of MMP-13 expression or activity, for inhalation may be a useful therapeutic strategy in diseases where repeated cycles of epithelial injury and repair occur, such as asthma and COPD.

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Leukotriene receptor antagonist attenuated airway inflammation and hyperresponsiveness in a double-stranded RNA-induced asthma exacerbation model

Abstract: This is the first report showing that LTRA functionally suppressed the pathophysiology of a virus-induced asthma exacerbation model, suggesting the importance of cysLTs as a potential treatment target.

Cited by 9 publications

References 34 publications

The non-antibiotic macrolide EM900 attenuates HDM and poly(I:C)-induced airway inflammation with inhibition of macrophages in a mouse model

The non-antibiotic macrolide EM900 attenuates HDM and poly(I:C)-induced airway inflammation with inhibition of macrophages in a mouse model

Emerging Role of Phospholipase-Derived Cleavage Products in Regulating Eosinophil Activity: Focus on Lysophospholipids, Polyunsaturated Fatty Acids and Eicosanoids

Targeting matrix metalloproteinase‐13 in bronchial epithelial repair

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