title: Linoleic acid metabolite drives severe asthma by causing airway epithelial injury.
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.
authors: Molecular Immunogenetics Laboratory and Centre of Excellence for Translational Research in Asthma and Lung Disease, CSIR-Institute of Genomics and Integrative Biology, India. um.rajan@igib.res.in
authors: Ulaganathan
authors: U
authors: Mabalirajan
authors: Rakhshinda
authors: R
authors: Rehman
authors: Tanveer
authors: T
authors: Ahmad
authors: Sarvesh
authors: S
authors: Kumar
authors: Suchita
authors: S
authors: Singh
authors: Geeta D
authors: GD
authors: Leishangthem
authors: Jyotirmoi
authors: J
authors: Aich
authors: Manish
authors: M
authors: Kumar
authors: Kritika
authors: K
authors: Khanna
authors: Vijay P
authors: VP
authors: Singh
authors: Amit K
authors: AK
authors: Dinda
authors: Shyam
authors: S
authors: Biswal
authors: Anurag
authors: A
authors: Agrawal
authors: Balaram
authors: B
authors: Ghosh
mesh_terms: D000818:Animals; D001249:Asthma / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D004195:Disease Models, Animal; D005110:Extracellular Space / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006801:Humans; D019787:Linoleic Acid / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008928:Mitochondria / Q000378:metabolism / Q000648:ultrastructure; D009504:Neutrophils / Q000276:immunology; D020545:Respiratory Mucosa / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D013045:Species Specificity; D050916:TRPV Cation Channels / Q000235:genetics / Q000378:metabolism
chemical_list: D005231:Fatty Acids, Unsaturated; D050916:TRPV Cation Channels; D019787:Linoleic Acid; D002118:Calcium