Activated T helper 17 (Th-17)
cytokines play a role in the pathophysiology of autoimmune and
infectious diseases. While these diseases affect many women of childbearing age, little is known about the effect of these
cytokines on placental transporters. As several pro-inflammatory
cytokines impact the expression of ABC and SLC placental transporters, we hypothesized that these transporters may be similarly altered by elevated levels of circulating Th-17
cytokines. Cultured term human villous explants were treated with
IL-17A,
IL-22, or
IL-23, alone or in combination. Samples were analyzed using qRT-PCR and Western blotting. The
mRNA expression of OATP2B1 was significantly downregulated in explants by all individual
cytokines and combination treatments, while decreased
protein expression was seen with
IL-23 and combination (p < 0.01). Combination treatment decreased the
mRNA expression of BCRP and OAT4 but increased that of OCT3 (p < 0.01). Decreased accumulation of the OATP substrate,
cascade blue, was seen in IL-23-treated
choriocarcinoma JAr cells (p < 0.01). Elevated Th-17
cytokines, which are seen in infectious and
autoimmune diseases, affect the expression and activity of OATP2B1, as well as
mRNA expression of placental BCRP, OAT4, and OCT3. This dysregulation could impact the fetal exposure to endogenous and exogenous substrates.