The role of 12/15-lipoxygenase in production of selected eicosanoids in allergic airway inflammation

Purpose: To evaluate the role of 12/15-lipoxygenase (LOX) in regulation of synthesis of selected eicosanoids in mice sensitized and challenged with Dermatophagoides pteronyssinus (Dp) allergen extract. Materials and methods: Both C57Bl and 12/15-LOX knockout mice were sensitized by 2 intraperitoneal injections and subsequently challenged by inhalation with Dp allergen extract. Sham sensitized and challenged mice were used as controls. Samples of bronchoalveolar lavage (BAL) were used for assessment of prostaglandin E2 (PGE2), cysteinyl leukotreienes (cysLT), lipoxin A4 (LXA4) and 15-hydroxyeicosatetraenoic acid (15-HETE) concentration using ELISA method. Whole lung samples were used for isolation of RNA and evaluation of selected genes involved in eicosanoid metabolism, including cyclooxygenase-2 (COX-2), 12/15-LOX, 5-LOX and 5-LOX activated protein (FLAP). Results: Allergen-induced airway inflammation was associated with significant (9-fold, 95% CI 8.0689.932- fold; p < 0.05) up-regulation of 12/15-LOX in wild type but not in the 12/15-LOX knockout mice in which 12/15-LOX mRNA remained undetectable. Lack of 12/15-LOX was associated with significant attenuation of production of 15-HETE in response to allergen challenge. On the contrary, the greatest up-regulation of COX-2 after allergen exposure was demonstrated in the 12/15-LOX knockout mice (4.3-fold vs sham group) and was significantly greater than in the wild type counterparts (5.185-fold, 95% CI 4.723-6.309-fold; p < 0.05 vs wild type mice). Also, allergen challenged 12/15-LOX knockout mice were characterized by greater production of PGE2 and cysLT. Conclusion: The 12/15-LOX plays an important role in the metabolism of eicosanoids in response to allergen-induced airway inflammation. (C) 2015 Medical University of Bialystok. Published by Elsevier Sp. z o.o. All rights reserved.