title: Eicosanoid biosynthesis during mucociliary and mucous metaplastic differentiation of bronchial epithelial cells.
abstract: The purpose of this study was to examine the profile of eicosanoids secreted by human bronchial epithelial cells (HBEC) during their in vitro differentiation toward mucociliary or mucous metaplastic phenotype. Eicosanoids were measured in supernatants by mass spectrometry, and corresponding gene expression by real-time PCR. Primary HBEC produced mainly prostaglandins (PGE2, PGD2) and epoxides (e.g. 14,15-EET), but during further mucociliary differentiation we observed a gradual increase in secretion of lipoxygenase derived HETEs. Treatment with IL-13 and IL-4 induced mucous metaplasia and resulted in downregulation of PG pathway, and potent induction of 15-lipoxygenase (marked release of 15-HETE). The deficiency in PG production sustained during long term culture of mucous metaplastic epithelia. In conclusions, Th2-type cytokines induce changes in eicosanoid metabolism of airway epithelial cells, resulting in an immense induction of 15-lipoxygenase pathway, and inhibition of PG pathways. Deficient production of immunomodulatory PGs may promote chronic inflammation and airway remodeling.
authors.affiliation: Department of Medicine, Jagiellonian University Medical College, ul. Skawinska 8, 31-066 Krakow, Poland. Electronic address: bogumil.j@poczta.fm.
authors.forename: Bogdan
authors.initials: B
authors.lastname: Jakiela
authors.forename: Anna
authors.initials: A
authors.lastname: Gielicz
authors.forename: Hanna
authors.initials: H
authors.lastname: Plutecka
authors.forename: Magdalena
authors.initials: M
authors.lastname: Hubalewska
authors.forename: Lucyna
authors.initials: L
authors.lastname: Mastalerz
authors.forename: Grazyna
authors.initials: G
authors.lastname: Bochenek
authors.forename: Jerzy
authors.initials: J
authors.lastname: Soja
authors.forename: Rafal
authors.initials: R
authors.lastname: Januszek
authors.forename: Jacek
authors.initials: J
authors.lastname: Musial
authors.forename: Marek
authors.initials: M
authors.lastname: Sanak
mesh_terms: D000328:Adult; D000368:Aged; D001980:Bronchi / Q000473:pathology*; D002454:Cell Differentiation / Q000187:drug effects; D015777:Eicosanoids / Q000096:biosynthesis* / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D005786:Gene Expression Regulation / Q000187:drug effects; D020397:Goblet Cells / Q000187:drug effects / Q000473:pathology*; D006801:Humans; D018793:Interleukin-13 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D008679:Metaplasia / Q000378:metabolism; D008875:Middle Aged; D010641:Phenotype
chemical_list: D015777:Eicosanoids; D018793:Interleukin-13; D015847:Interleukin-4
keywords: 15-Lipoxygenase; Airway epithelium; Eicosanoids; Goblet cell metaplasia; Th2 cytokines