title: A role of prostaglandin transporter in regulating PGE₂ release from human bronchial epithelial BEAS-2B cells in response to LPS.
abstract: Naturally occurring prostaglandin E₂ (PGE₂) plays a role in inflammatory responses through eicosanoid signaling pathways. PGE₂ is impermeable to cell membranes at physiological pH and needs solute carrier across the membranes; however, it remains unclear how intercellular concentrations of PGE₂ are regulated under the condition of inflammation. We aimed to clarify a role of organic anion-transporting polypeptide 2A1 (OATP2A1/SLCO2A1), also known as prostaglandin transporter (PGT), in PGE₂ release from cells. Human bronchial epithelial BEAS-2B cells were treated with lipopolysaccharide (LPS), and PGT inhibitors were tested to evaluate contribution of PGT to PGE₂ release by assessing its extracellular concentration and characterizing PGT-mediated PGE₂ efflux in Xenopus laevis oocytes. As a result, LPS elevated mRNA expression of a pro-inflammatory cytokine IL6 and extracellular concentration of PGE₂ in human bronchial epithelial BEAS-2B cells. PGT inhibitors tested (e.g. bromocresol green (BCG), bromosulfophthalein (BSP), and PGB₁) significantly inhibited efflux of PGE₂ from oocytes expressing PGT. Similarly, the amount of released PGE2 from the BEAS-2B cells decreased in the presence of BCG and BSP by 45 and 44% respectively while TGBz increased the concentration by 71%, suggesting that PGT mediates the release. In conclusion, these results imply a role of PGT in regulating intra- and extracellular concentrations of PGE₂ in response to cells under inflammatory conditions.
authors.affiliation: Faculty of Pharmacy, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Shirasaka
authors.forename: Megumi
authors.initials: M
authors.lastname: Shichiri
authors.forename: Taku
authors.initials: T
authors.lastname: Kasai
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Ohno
authors.forename: Takeo
authors.initials: T
authors.lastname: Nakanishi
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Hayashi
authors.forename: Akio
authors.initials: A
authors.lastname: Nishiura
authors.forename: Ikumi
authors.initials: I
authors.lastname: Tamai
mesh_terms: D041721:3T3-L1 Cells; D000818:Animals; D001980:Bronchi / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002460:Cell Line; D015232:Dinoprostone / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D027361:Organic Anion Transporters / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D014982:Xenopus laevis
chemical_list: D015850:Interleukin-6; D008070:Lipopolysaccharides; D027361:Organic Anion Transporters; C503526:SLCO2A1 protein, human; D015232:Dinoprostone