Urocortin increases IL-4 and IL-10 secretion and reverses LPS-induced TNF-alpha release from human trophoblast primary cells

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. © 2009 John Wiley and Sons A/S. Cytokines; Inflammation; Placenta; Urocortin