IFN-γ-mediated inhibition of COX-2 expression in the placenta from term and preterm labor pregnancies

Nazeeh Hanna, Lea Bonifacio, Pradeep Reddy, Iman Hanna, Barry Weinberger, Shaun Murphy, Debra Laskin, Surendra Sharma

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

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 PGE 2 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.

Original languageEnglish (US)
Pages (from-to)311-318
Number of pages8
JournalAmerican Journal of Reproductive Immunology
Volume51
Issue number4
StatePublished - Apr 2004

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Reproductive Medicine
  • Obstetrics and Gynecology

Keywords

  • Cytokines
  • Placenta
  • Preterm labor
  • Prostaglandin biosynthesis

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