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.