Effects of urocortin 2 and urocortin 3 on IL-10 and TNF-α expression and secretion from human trophoblast explants

BJECTIVES: The aim of the present study was to evaluate the effect of Ucn2 and Ucn3 on cytokine expression and secretion from placental explants. STUDY DESIGN: Placentas were collected from healthy pregnancies at term elective caesarean delivery and trophoblast explants were prepared and treated with Ucn2 or Ucn3 in presence/absence of the selective CRH-R2 antagonist, astressin 2b. The mRNA expression and secretion of IL-10 and TNF-α were evaluated by Real Time RT-PCR and ELISA, respectively. MAIN OUTCOME MEASURES: To evaluate the possible role of Ucn2 and Ucn3 in inflammatory pathways. RESULTS: Ucn2 increased the mRNA expression and secretion of IL-10 and TNF-α, and Ucn3 increased the mRNA expression and secretion of IL-10, but did not modify the secretion of TNF-α. Ucn3 treatment reversed the LPS-induce increase of TNF-α expression and release, an effect blocked by astressin 2b. Ucn2 potentiated the LPS-induced increase of TNF-α expression and release, an effect reversed by astressin 2b. CONCLUSIONS: The present study showed that Ucn2 and Ucn3 differentially regulate the LPS-induced TNF-α and IL-10 expression and secretion in trophoblast explants acting through CRH-R2. A pro inflammatory effect of Ucn2 and an anti-inflammatory effect of Ucn3 in placental immunomodulatory mechanisms is suggested.