title: 12/15-lipoxygenase expressed in non-epithelial cells causes airway epithelial injury in asthma.
abstract: The mechanisms underlying asthmatic airway epithelial injury are not clear. 12/15-lipoxygenase (an ortholog of human 15-LOX-1), which is induced by IL-13, is associated with mitochondrial degradation in reticulocytes at physiological conditions. In this study, we showed that 12/15-LOX expressed in nonepithelial cells caused epithelial injury in asthma pathogenesis. While 12/15-LOX overexpression or IL-13 administration to naïve mice showed airway epithelial injury, 12/15-LOX knockout/knockdown in allergic mice reduced airway epithelial injury. The constitutive expression of 15-LOX-1 in bronchial epithelia of normal human lungs further indicated that epithelial 15-LOX-1 may not cause epithelial injury. 12/15-LOX expression is increased in various inflammatory cells in allergic mice. Though non-epithelial cells such as macrophages or fibroblasts released 12/15-LOX metabolites upon IL-13 induction, bronchial epithelia didn't release. Further 12-S-HETE, arachidonic acid metabolite of 12/15-LOX leads to epithelial injury. These findings suggested 12/15-LOX expressed in non-epithelial cells such as macrophages and fibroblasts leads to bronchial epithelial injury.
authors.affiliation: Molecular Immunogenetics Laboratory and Centre of Excellence for Translational Research in Asthma & Lung disease, CSIR-Institute of Genomics and Integrative Biology, Mall Road, Delhi-110007, India. um.rajan@igib.res.in
authors.forename: Ulaganathan
authors.initials: U
authors.lastname: Mabalirajan
authors.forename: Rakhshinda
authors.initials: R
authors.lastname: Rehman
authors.forename: Tanveer
authors.initials: T
authors.lastname: Ahmad
authors.forename: Sarvesh
authors.initials: S
authors.lastname: Kumar
authors.forename: Geeta Devi
authors.initials: GD
authors.lastname: Leishangthem
authors.forename: Suchita
authors.initials: S
authors.lastname: Singh
authors.forename: Amit Kumar
authors.initials: AK
authors.lastname: Dinda
authors.forename: Shyam
authors.initials: S
authors.lastname: Biswal
authors.forename: Anurag
authors.initials: A
authors.lastname: Agrawal
authors.forename: Balaram
authors.initials: B
authors.lastname: Ghosh
mesh_terms: D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid / Q000097:blood / Q000276:immunology / Q000378:metabolism; D016475:3T3 Cells; D000818:Animals; D001092:Arachidonate 12-Lipoxygenase / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D001093:Arachidonate 15-Lipoxygenase / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D001249:Asthma / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015153:Blotting, Western; D002460:Cell Line; D045304:Cytochromes c / Q000276:immunology / Q000378:metabolism; D004848:Epithelium / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D005347:Fibroblasts / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D018793:Interleukin-13 / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology; D007783:Lactones; D008041:Linoleic Acids / Q000097:blood / Q000276:immunology / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000648:ultrastructure; D008264:Macrophages / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D008928:Mitochondria / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D045787:Sesquiterpenes, Eudesmane
chemical_list: C475064:12-15-lipoxygenase; C505182:13-sulfo-dihydroreynosin; D018793:Interleukin-13; D007783:Lactones; D008041:Linoleic Acids; D045787:Sesquiterpenes, Eudesmane; C024348:13-hydroxy-9,11-octadecadienoic acid; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D045304:Cytochromes c; D001092:Arachidonate 12-Lipoxygenase; D001093:Arachidonate 15-Lipoxygenase