title: On the biosynthesis of 15-HETE and eoxin C4 by human airway epithelial cells.
abstract: Several lines of evidence indicate that 15-lipoxygenase type 1 (15-LO-1) plays a pathophysiological role in asthma. The aim for this study was to investigate the 15-LO-1 expression and activity in primary human airway epithelial cells cultivated on micro-porous filters at air-liquid interface. Incubation of human airway epithelial cells with arachidonic acid led to the formation of 15(S)-hydroxy-eicosatetraenoic acid (15-HETE) and exposing the cells to bacteria or physical injury markedly increased their production of 15-HETE. The cells were also found to convert arachidonic acid to eoxin C4 (EXC4). Subcellular fractionation revealed that the conversion of EXA4 to EXC4 was catalyzed by a soluble glutathione transferase (GST). The GST P1-1 enzyme was found to possess the highest activity of the investigated soluble GSTs. Following IL-4 treatment of airway epithelial cells, microarray analysis confirmed high expression of 15-LO-1 and GST P1-1, and immunohistochemical staining of bronchial biopsies revealed co-localization of 15-LO-1 and GST P1-1 in airway epithelial cells. These results indicate that respiratory infection and cell injury may activate the 15-LO pathway in airway epithelial cells. Furthermore, we also demonstrate that airway epithelial cells have the capacity to produce EXC4.
authors.affiliation: Department of Medicine, Karolinska University Hospital and Karolinska Institutet, SE-171 76 Stockholm, Sweden.
authors.forename: Åsa
authors.initials: Å
authors.lastname: Brunnström
authors.affiliation: Orexo AB, Box 303, SE-751 05 Uppsala, Sweden.
authors.forename: Ylva
authors.initials: Y
authors.lastname: Tryselius
authors.affiliation: Orexo AB, Box 303, SE-751 05 Uppsala, Sweden.
authors.forename: Stina
authors.initials: S
authors.lastname: Feltenmark
authors.affiliation: Orexo AB, Box 303, SE-751 05 Uppsala, Sweden.
authors.forename: Erik
authors.initials: E
authors.lastname: Andersson
authors.affiliation: Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Sweden.
authors.forename: Helene
authors.initials: H
authors.lastname: Leksell
authors.affiliation: Institute of Environmental Medicine, Karolinska Institutet, Sweden; The Centre for Allergy Research, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: James
authors.affiliation: Department of Neurochemistry, Stockholm University, SE-10691 Stockholm, Sweden.
authors.forename: Bengt
authors.initials: B
authors.lastname: Mannervik
authors.affiliation: The Centre for Allergy Research, Sweden; Department of Medicine, Karolinska University Hospital Huddinge, Sweden.
authors.forename: Barbro
authors.initials: B
authors.lastname: Dahlén
authors.affiliation: Department of Medicine, Karolinska University Hospital and Karolinska Institutet, SE-171 76 Stockholm, Sweden. Electronic address: hans-erik.claesson@ki.se.
authors.forename: Hans-Erik
authors.initials: HE
authors.lastname: Claesson
mesh_terms: D001093:Arachidonate 15-Lipoxygenase / Q000378:metabolism; D016718:Arachidonic Acid / Q000378:metabolism; D055162:Biocatalysis; D001980:Bronchi / Q000166:cytology*; D002460:Cell Line; D004847:Epithelial Cells / Q000378:metabolism*; D005982:Glutathione Transferase / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000096:biosynthesis*; D015289:Leukotrienes / Q000096:biosynthesis*; D021381:Protein Transport; D012995:Solubility
chemical_list: D006893:Hydroxyeicosatetraenoic Acids; D015289:Leukotrienes; C526311:eoxin C4; D016718:Arachidonic Acid; C025984:15-hydroxy-5,8,11,13-eicosatetraenoic acid; C515716:ALOX15 protein, human; D001093:Arachidonate 15-Lipoxygenase; D005982:Glutathione Transferase
keywords: 15-HETE; 15-Lipoxygenase; Airway epithelial cells; Asthma; Eoxin C(4); Glutathione transferase; Pseudomonas aeruginosa