Impact of Th-17 Cytokines on the Regulation of Transporters in Human Placental Explants
| Autor: | Ori Nevo, Micheline Piquette-Miller, Kamelia Mirdamadi, Howard Berger, Jacinda Kwok |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
medicine.medical_specialty
placenta Pharmaceutical Science Endogeny Inflammation drug transporters Biology Article 03 medical and health sciences 0302 clinical medicine Pharmacy and materia medica Placenta Internal medicine explants medicine 030304 developmental biology 0303 health sciences Choriocarcinoma Transporter Th-17 medicine.disease Pathophysiology cytokines Blot RS1-441 medicine.anatomical_structure Endocrinology inflammation 030220 oncology & carcinogenesis Interleukin 17 medicine.symptom interleukin 17 |
| Zdroj: | Pharmaceutics Pharmaceutics, Vol 13, Iss 881, p 881 (2021) Volume 13 Issue 6 |
| ISSN: | 1999-4923 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|