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


METHODS
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.


CONCLUSIONS
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.
Torricelli
Michela
M
Obstetrics and Gynecology, Department of Pediatrics, Obstetrics and Reproductive Medicine, University of Siena, Siena, Italy.
Voltolini
Chiara
C
Bloise
Enrrico
E
Biliotti
Giulia
G
Giovannelli
Alessia
A
De Bonis
Maria
M
Imperatore
Alberto
A
Petraglia
Felice
F
D018929:Cell Culture Techniques; D004305:Dose-Response Relationship, Drug; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism*; D015847:Interleukin-4 / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D011247:Pregnancy; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors; D014327:Trophoblasts / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D054832:Urocortins / Q000378:metabolism* / Q000494:pharmacology
D008070:Lipopolysaccharides; D010446:Peptide Fragments; D010456:Peptides, Cyclic; D018019:Receptors, Corticotropin-Releasing Hormone; D014409:Tumor Necrosis Factor-alpha; D054832:Urocortins; C528574:astressin-2B; D016753:Interleukin-10; D015847:Interleukin-4