Surendra Sharma, Women and Infants’ Hospital, Dept. of Pediatrics, 101 Dudley Street, Providence, RI 02905, USA E-mail: email@example.com
IFN-γ-Mediated Inhibition of COX-2 Expression in the Placenta from Term and Preterm Labor Pregnancies
Version of Record online: 16 MAR 2004
American Journal of Reproductive Immunology
Volume 51, Issue 4, pages 311–318, April 2004
How to Cite
Hanna, N., Bonifacio, L., Reddy, P., Hanna, I., Weinberger, B., Murphy, S., Laskin, D. and Sharma, S. (2004), IFN-γ-Mediated Inhibition of COX-2 Expression in the Placenta from Term and Preterm Labor Pregnancies. American Journal of Reproductive Immunology, 51: 311–318. doi: 10.1111/j.1600-0897.2004.00162.x
- Issue online: 16 MAR 2004
- Version of Record online: 16 MAR 2004
- Submitted November 15, 2003; accepted December 8, 2003.
- preterm labor;
- prostaglandin biosynthesis
Problem: The inflammatory-anti-inflammatory cytokine network is thought to play a critical role in regulated progression and termination of pregnancy. The aim of this study was to evaluate the effects of interferon (IFN)-γ on the expression of Cyclooxygenase (COX)-2 and production of prostaglandin E2 (PGE2) in the human placenta from term and preterm labor deliveries.
Method of study: Placental explant culture system was used. COX-2 expression was determined by complementary techniques of immunohistochemistry and Western blotting. Released IFN-γ and PGE2 by placental explants were measured by enzyme-linked immunosorbent assay. Signal transducer and activator of transcription 1 (STAT1) phosphorylation was evaluated by Western blotting using a specific antibody.
Results: IFN-γ was poorly detected in the placenta but was significantly expressed in decidual tissues from both term and preterm pregnancies as detected by immunohistochemistry. IFN-γ significantly inhibited COX-2 expression and PGE2 release in cultured placental explants from term and preterm labor deliveries. This effect most likely occurred in a STAT1-dependent manner as this regulatory protein was phosphorylated in response to IFN-γ. IFN-γ receptor (IFN-γR) was expressed in normal early pregnancy placental samples. However, its expression was significantly reduced in placental samples from term and preterm deliveries. Of interest, IFN-γR was expressed in placentas from term and preterm labor deliveries after 24 hr in culture.
Conclusions: Our data suggest that the human placenta is an important site for IFN-γ-mediated repression of COX-2 expression and PGE2 production, implying that functional withdrawal of IFN-γ may be involved in the onset of term or preterm labor.