Molecular Human Reproduction, Vol. 9, No. 1, 1-8,
January 2003
© 2003 European Society of Human Reproduction and Embryology
Article |
Interleukin-1ß induces glycosaminoglycan synthesis via the prostaglandin E2 pathway in cultured human cervical fibroblasts
Submitted on February 7, 2002; resubmitted on August 7, 2002. accepted on October 31, 2002
1 INSERM U 361, Université René Descartes, Paris and 2 Maternité Port-Royal, Hopital Cochin, AP-HP, Université René Descartes, Paris, France 3 To whom correspondence should be addressed at: INSERM U 361, Pavillon Baudelocque, 123, Bd de Port-Royal, F-75014 Paris, France. e-mail: tsn{at}club-internet.fr
The aim of this study was to identify, in cultured human cervical fibroblasts, the mechanisms by which interleukin (IL)-1ß induces the synthesis of glycosaminoglycans (GAG) and to explore the putative role of prostaglandin E2 (PGE2) in this process. Exposure of the cells for 24 h to IL-1ß induced a significant (P < 0.05) dose-dependent increase in GAG synthesis. IL-1ß (1 ng/ml) induced the expression of cyclooxygenase-2 (COX-2) protein 6 h after treatment, accompanied by a 7.5-fold increase in PGE2 production. We confirmed that NS398, a selective COX-2 inhibitor, dose-dependently blocked PGE2 augmentation following IL-1ß treatment. AH23848, the selective EP4 receptor antagonist, completely abolished IL-1ß-induced GAG synthesis, whereas AH6809, an EP2 receptor antagonist, had no effect on the stimulatory effects of IL-1ß. Furthermore, we demonstrated that 6 h exposure to IL-1ß induced a notable increase in EP4 receptor mRNA expression and a decrease in EP1 receptor mRNA but had no effect on the expression of EP2 and EP3 receptor transcripts. In conclusion, these findings indicate that IL-1ß not only induced GAG synthesis by increasing COX-2 protein expression and the subsequent PGE2 production but also enhanced the responsiveness of cervical fibroblasts to PGE2 by selectively up-regulating EP4 receptor mRNA expression. These results suggest that PGE2 may regulate human cervical ripening in an autocrine/paracrine manner via EP4 receptors.
Key words: cervical ripening/EP receptors/glycosaminoglycan/IL-1ß/prostaglandin E2
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  N. Foudi, L. Louedec, T. Cachina, C. Brink, and X. Norel Selective cyclooxygenase-2 inhibition directly increases human vascular reactivity to norepinephrine during acute inflammation Cardiovasc Res, February 1, 2009; 81(2): 269 - 277. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A.A Fouladi-Nashta, L Mohamet, J.K Heath, and S.J Kimber Interleukin 1 Signaling Is Regulated by Leukemia Inhibitory Factor (LIF) and Is Aberrant in Lif-/- Mouse Uterus Biol Reprod, July 1, 2008; 79(1): 142 - 153. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Schmitz, B. A Levine, and P. W Nathanielsz Localization and steroid regulation of prostaglandin E2 receptor protein expression in ovine cervix. Reproduction, April 1, 2006; 131(4): 743 - 750. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R Largo, I Diez-Ortego, O Sanchez-Pernaute, M J Lopez-Armada, M A Alvarez-Soria, J Egido, and G Herrero-Beaumont EP2/EP4 signalling inhibits monocyte chemoattractant protein-1 production induced by interleukin 1{beta} in synovial fibroblasts Ann Rheum Dis, October 1, 2004; 63(10): 1197 - 1204. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Zaga, G. Estrada-Gutierrez, J. Beltran-Montoya, R. Maida-Claros, R. Lopez-Vancell, and F. Vadillo-Ortega Secretions of Interleukin-1{beta} and Tumor Necrosis Factor {alpha} by Whole Fetal Membranes Depend on Initial Interactions of Amnion or Choriodecidua with Lipopolysaccharides or Group B Streptococci Biol Reprod, October 1, 2004; 71(4): 1296 - 1302. [Abstract] [Full Text] [PDF]
|
|