Journal
PROSTAGLANDINS & OTHER LIPID MEDIATORS
Volume 137, Issue -, Pages 20-29Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.prostaglandins.2018.05.005
Keywords
BALF; HDM; PUFA; Lipid mediators; Airway hyperresponsiveness
Categories
Funding
- Sistema Riojano de Innovacion (Gobierno de La Rioja, Spain)
- Fundacion Rioja Salud (Gobierno de La Rioja, Spain)
- Swedish Heart-Lung Foundation [20150525, 20130636, 20150640, 20140469, 20140533]
- Swedish Research Council [2016-02798, 2014-3281]
- Konsul Th C Berghs research foundation
- ChAMP (Centre for Allergy Research Highlights Asthma Markers of Phenotype) consortium
- Swedish Foundation for Strategic Research
- Karolinska Institutet
- AstraZeneca
- Science for Life Laboratory Joint Research Collaboration
- Vardal Foundation
- European Cooperation in Science and Technology COST Action [BM1201]
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The profile of activation of lipid mediator (LM) pathways in asthmatic airway inflammation remains unclear. This experimental study quantified metabolite levels of omega 3-, omega 6- and omega 9-derived polyunsaturated fatty acids in bronchoalveolar lavage fluid (BALF) after 4-weeks of repeated house dust mite (HDM) exposure in a murine (C57BL/6) asthma model. The challenge induced airway hyperresponsiveness, pulmonary eosinophil infiltration, but with low and unchanged mast cell numbers. Of the 112 screened LMs, 26 were increased between 2 to > 25-fold in BALF with HDM treatment (p < 0.05, false discovery rate = 5%). While cysteinyl-leukotrienes were the most abundant metabolites at baseline, their levels did not increase after HDM treatment, whereas elevation of PGD(2), LTB4 and multiple 12/15-lipoxygenase products, such as 5,15-DiHETE, 15-HEDE and 15-HEPE were observed. We conclude that this model has identified a global lipoxygenase activation signature, not linked to mast cells, but with aspects that mimic chronic allergic airway inflammation in asthma.
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