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

Am J Reprod Immunol. 2009 Oct;62(4):224-31. doi: 10.1111/j.1600-0897.2009.00729.x. Epub 2009 Aug 24.

Abstract

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-alpha 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-alpha secretion. When incubated in the presence of LPS, Ucn reversed LPS-induced TNF-alpha 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-alpha release from trophoblast cells through action on CRH-R2 receptors, suggesting that this peptide may play a possible role as an anti-inflammatory agent.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Culture Techniques
  • Dose-Response Relationship, Drug
  • Female
  • Gene Expression Regulation / drug effects
  • Humans
  • Interleukin-10 / metabolism*
  • Interleukin-4 / metabolism*
  • Lipopolysaccharides / pharmacology
  • Peptide Fragments / pharmacology
  • Peptides, Cyclic / pharmacology
  • Pregnancy
  • Receptors, Corticotropin-Releasing Hormone / antagonists & inhibitors
  • Trophoblasts / drug effects
  • Trophoblasts / immunology
  • Trophoblasts / metabolism*
  • Trophoblasts / pathology
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / immunology
  • Tumor Necrosis Factor-alpha / metabolism*
  • Urocortins / metabolism*
  • Urocortins / pharmacology

Substances

  • Lipopolysaccharides
  • Peptide Fragments
  • Peptides, Cyclic
  • Receptors, Corticotropin-Releasing Hormone
  • Tumor Necrosis Factor-alpha
  • Urocortins
  • astressin-2B
  • Interleukin-10
  • Interleukin-4