Independent regulation of apical and basolateral drug transporter expression and function in placental trophoblasts by cytokines, steroids, and growth factors. Drug Metab. Dispos

Placental ATP binding cassette (ABC) transporters protect placen-tal and fetal tissues by effluxing xenobiotics and endogenous me-tabolites. We have investigated the effects of cytokines and sur-vival/growth factors, implicated in various placental pathologies, on ABC transporter expression and function in primary placental trophoblast cells. Treatment of primary term trophoblasts in vitro with tumor necrosis factor- (TNF-) or interleukin (IL)-1 de-creased mRNA and protein expression of apical transporters ABCB1/multidrug resistance gene product 1 (MDR1) and ABCG2/ breast cancer resistance protein (BCRP) protein by 40 to 50 % (P < 0.05). In contrast, IL-6 increased mRNA and protein expression of the basolateral transporter ABCB4/MDR3 (P < 0.05), whereas ABCC1/MRP1 expression was unaltered. Pretreatment of tropho-blasts with TNF- over 48 h resulted in significantly decreased BCRP efflux activity (increased mitoxantrone accumulation) wit