Linoleic acid metabolite drives severe asthma by causing airway epithelial injury

Molecular Immunogenetics Laboratory and Centre of Excellence for Translational Research in Asthma and Lung Disease, CSIR-Institute of Genomics and Integrative Biology, India.
Scientific Reports (Impact Factor: 5.08). 02/2013; 3:1349. DOI: 10.1038/srep01349
Source: PubMed

ABSTRACT Airway epithelial injury is the hallmark of various respiratory diseases, but its mechanisms remain poorly understood. While 13-S-hydroxyoctadecadienoic acid (13-S-HODE) is produced in high concentration during mitochondrial degradation in reticulocytes little is known about its role in asthma pathogenesis. Here, we show that extracellular 13-S-HODE induces mitochondrial dysfunction and airway epithelial apoptosis. This is associated with features of severe airway obstruction, lung remodeling, increase in epithelial stress related proinflammatory cytokines and drastic airway neutrophilia in mouse. Further, 13-S-HODE induced features are attenuated by inhibiting Transient Receptor Potential Cation Channel, Vanilloid-type 1 (TRPV1) both in mouse model and human bronchial epithelial cells. These findings are relevant to human asthma, as 13-S-HODE levels are increased in human asthmatic airways. Blocking of 13-S-HODE activity or disruption of TRPV1 activity attenuated airway injury and asthma mimicking features in murine allergic airway inflammation. These findings indicate that 13-S-HODE induces mitochondrial dysfunction and airway epithelial injury.

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    ABSTRACT: Background Etiology and pathogenesis of bronchial asthma remain unclear. This study is to investigate risk factors related to bronchial asthma onset in children from genetics and immunology and preliminarily reveal pathogenesis of bronchial asthma in children.Methods Real-time quantification PCR was adopted to detect expression level of TRPV1 gene and mRNA and ELISA method to the total IgE level and levels of IL-4, IL-5 and IFN-γ in serum in peripheral venous blood for children in two groups. Logistic regression analysis was applied to analyze the most essential factors inducing bronchial asthma in children.ResultsmRNA level of TRPV1 in peripheral blood in case group was higher than that in control group (p<0.01). Levels of IL-4, IL-5 and EOS in serum in case group were markedly higher than those in control group (p<0.01), while IFN-γ level was lower than that in control group (p<0.01). Results of logistic regression analysis indicated that TRPV1 expression level, IL-4 level and rs4790522 site mutation were the main risk factors inducing bronchial asthma in children.Conclusions Levels of TRPV1 gene expression and Th1/Th2 cytokines have a close relationship with asthma onset in children, which provides theoretical evidences for molecular targeted treatment in children with bronchial asthma.Pediatric Research (2015); doi:10.1038/pr.2015.11.
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