Linoleic acid metabolite drives severe asthma by causing airway epithelial injury
Mabalirajan U, Rehman R, Ahmad T, Kumar S, Singh S, Leishangthem GD, Aich J, Kumar M, Khanna K, Singh VP, Dinda AK, Biswal S, Agrawal A, Ghosh B
Scientific reports · 99 citations
How it was studied
- Design
- Animal study (classified by our AI screen)
- Studied in
- People, plus animal or lab work
- Main outcome
- Health markers and function
Who paid for it
- Funding
- Independent funding
- Government
- Council of Scientific and Industrial Research, India
- Grants
- Council of Scientific and Industrial Research, India (MLP5502)
Based on 1 listed funder(s) and full-text disclosure statement.
Publication
- Published
- 2013-02-27 · Sci Rep · vol. 3 · issue 1 · p. 1349
- Publisher
- Nature Portfolio
- Cited
- 116 citations · more than 96% of similar papers · 5.3× the field average
- Impact
- Top 10% most cited in its field
- References
- 47 works
- Access
- Open access (journal) · CC-BY-NC-ND
- Research areas
- Asthma and respiratory diseases · Ion Channels and Receptors · Respiratory and Cough-Related Research
- Keywords
- Proinflammatory cytokine, Airway, Medicine, Neutrophilia, Asthma, Inflammation, Immunology, TRPV1, Respiratory epithelium, Lung, Bronchoconstriction, Pathogenesis, Transient receptor potential channel, Receptor, Anesthesia, Internal medicine
- MeSH
- respiratory mucosa, neutrophils, extracellular space, mitochondria, animals, mice, inbred balb c, humans, mice, asthma, disease models, animal, calcium, fatty acids, unsaturated, linoleic acid, species specificity, trpv cation channels, gene knockdown techniques
14 authors
From IN, US
- Ulaganathan MabalirajanInstitute of Genomics and Integrative Biology
- Rakhshinda RehmanInstitute of Genomics and Integrative Biology
- Tanveer AhmadInstitute of Genomics and Integrative Biology
- Sarvesh KumarJohns Hopkins University
- Suchita SinghInstitute of Genomics and Integrative Biology
- Geeta Devi LeishangthemAll India Institute of Medical Sciences
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.
Abstract via Europe PMC. Copyright remains with the authors or publisher (CC BY-NC-ND).
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