title: The role of 12/15-lipoxygenase in production of selected eicosanoids in allergic airway inflammation.
abstract: OBJECTIVE
  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.
  
  
  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 8.068-9.932-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.
  
  
  CONCLUSIONS
  The 12/15-LOX plays an important role in the metabolism of eicosanoids in response to allergen-induced airway inflammation.
authors.affiliation: Center of Experimental Medicine, Medical University of Bialystok, Białystok, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Sacharzewska
authors.affiliation: Department of Molecular Biology, Medical University of Bialystok, Białystok, Poland; Department of Otolaryngology, Provincial Specialist Hospital in Bialystok, Białystok, Poland.
authors.forename: Pawel
authors.initials: P
authors.lastname: Bielecki
authors.affiliation: Department of Molecular Biology, Medical University of Bialystok, Białystok, Poland.
authors.forename: Pawel
authors.initials: P
authors.lastname: Bernatowicz
authors.affiliation: Department of Molecular Biology, Medical University of Bialystok, Białystok, Poland.
authors.forename: Jacek
authors.initials: J
authors.lastname: Niklinski
authors.affiliation: Department of Rheumatology and Internal Medicine, Medical University of Bialystok, Białystok, Poland.
authors.forename: Otylia
authors.initials: O
authors.lastname: Kowal-Bielecka
authors.affiliation: Department of Allergology and Internal Medicine, Medical University of Bialystok, Białystok, Poland; Department of Experimental Allergology and Immunology, Medical University of Bialystok, Białystok, Poland. Electronic address: kowalkmd@umb.edu.pl.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Kowal
mesh_terms: D000818:Animals; D039741:Antigens, Dermatophagoides; D001092:Arachidonate 12-Lipoxygenase / Q000378:metabolism*; D001093:Arachidonate 15-Lipoxygenase / Q000378:metabolism*; D053898:Biosynthetic Pathways / Q000235:genetics; D001992:Bronchoalveolar Lavage Fluid; D015777:Eicosanoids / Q000096:biosynthesis*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006967:Hypersensitivity / Q000150:complications* / Q000201:enzymology*; D007073:Immunoglobulin E / Q000096:biosynthesis; D008168:Lung / Q000201:enzymology / Q000473:pathology; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011014:Pneumonia / Q000150:complications* / Q000201:enzymology*
chemical_list: C475064:12-15-lipoxygenase; D039741:Antigens, Dermatophagoides; D015777:Eicosanoids; D007073:Immunoglobulin E; D001092:Arachidonate 12-Lipoxygenase; D001093:Arachidonate 15-Lipoxygenase
keywords: 12/15-Lipoxygenase; Allergic airway inflammation; Eicosanoids; Knockout mice