ORIGINAL ARTICLE: Urocortin Increases IL-4 and IL-10 Secretion and Reverses LPS-induced TNF-α Release from Human Trophoblast Primary Cells


Felice Petraglia, Obstetrics and Gynecology, Department of Pediatrics, Obstetrics and Reproductive Medicine, University of Siena, “S. Maria alle Scotte”, viale Bracci 53100 Siena, Italy.
E-mail: petraglia@unisi.it


Problem  As urocortin (Ucn) is a placental peptide belonging to the corticotrophin-releasing hormone (CRH) family that modulates immune function in other biological models, this study evaluated Ucn effects on cytokines secretion from cultured human trophoblast cells.

Method of study  Placentas were collected from normal term pregnancies after elective caesarean section, and primary trophoblast culture was prepared followed by the treatment of Ucn and/or CRH selective antagonists, antalarmin and astressin 2b. The anti-inflammatory cytokines IL-4 and IL-10 and the pro-inflammatory cytokine TNF-α were measured by ELISA.

Results  Urocortin treatment induced a significant and dose-dependent increase of IL-4 and IL-10, whereas it did not affect TNF-α secretion. When incubated in the presence of LPS, Ucn reversed LPS-induced TNF-α release from cultured trophoblast cells, an effect that was blocked by the CRH-R2 selective antagonist, astressin 2b.

Conclusion  Urocortin stimulates IL-4 and IL-10 secretion and reverses LPS-induced TNF-α release from trophoblast cells through action on CRH-R2 receptors, suggesting that this peptide may play a possible role as an anti-inflammatory agent.