Prominent release of lipoxygenase generated mediators in a murine house dust mite-induced asthma model

Publication date: July 2018Source: Prostaglandins & Other Lipid Mediators, Volume 137Author(s): Johan Kolmert, Sergio Piñeiro-Hermida, Mats Hamberg, Joshua A. Gregory, Icíar P. López, Alexander Fauland, Craig E. Wheelock, Sven-Erik Dahlén, José G. Pichel, Mikael AdnerAbstractThe profile of activation of lipid mediator (LM) pathways in asthmatic airway inflammation remains unclear. This experimental study quantified metabolite levels of ω3-, ω6- and ω9-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 PGD2, 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.
Source: Prostaglandins and Other Lipid Mediators - Category: Lipidology Source Type: research