IFN-gamma-mediated inhibition of COX-2 expression in the placenta from term and preterm labor pregnancies.
OBJECTIVE
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)-gamma on the expression of Cyclooxygenase (COX)-2 and production of prostaglandin E(2) (PGE(2)) in the human placenta from term and preterm labor deliveries.


METHODS
Placental explant culture system was used. COX-2 expression was determined by complementary techniques of immunohistochemistry and Western blotting. Released IFN-gamma 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-gamma was poorly detected in the placenta but was significantly expressed in decidual tissues from both term and preterm pregnancies as detected by immunohistochemistry. IFN-gamma significantly inhibited COX-2 expression and PGE(2) 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-gamma. IFN-gamma receptor (IFN-gammaR) 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-gammaR 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-gamma-mediated repression of COX-2 expression and PGE2 production, implying that functional withdrawal of IFN-gamma may be involved in the onset of term or preterm labor.
Hanna
Nazeeh
N
Division of Neonatology, Department of Pediatrics, UMDNJ-Robert Wood, Johnson Medical School, New Brunswick, NJ 08903, USA. hannann@umdnj.edu
Bonifacio
Lea
L
Reddy
Pradeep
P
Hanna
Iman
I
Weinberger
Barry
B
Murphy
Shaun
S
Laskin
Debra
D
Sharma
Surendra
S
D000293:Adolescent; D000328:Adult; D015153:Blotting, Western; D051546:Cyclooxygenase 2; D004268:DNA-Binding Proteins / Q000032:analysis / Q000378:metabolism; D003656:Decidua / Q000737:chemistry; D015232:Dinoprostone / Q000032:analysis / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000032:analysis / Q000494:pharmacology / Q000502:physiology*; D007527:Isoenzymes / Q000032:analysis / Q000378:metabolism*; D007743:Labor, Obstetric; D008565:Membrane Proteins; D007752:Obstetric Labor, Premature; D010766:Phosphorylation; D010920:Placenta / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D011247:Pregnancy; D011261:Pregnancy Trimester, First / Q000378:metabolism; D011262:Pregnancy Trimester, Second / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000032:analysis / Q000378:metabolism*; D017471:Receptors, Interferon / Q000032:analysis / Q000378:metabolism; D050794:STAT1 Transcription Factor; D015534:Trans-Activators / Q000032:analysis / Q000378:metabolism; D000096743:Interferon gamma Receptor
D051546:Cyclooxygenase 2; D004268:DNA-Binding Proteins; D015232:Dinoprostone; D007371:Interferon-gamma; D007527:Isoenzymes; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases; D017471:Receptors, Interferon; D050794:STAT1 Transcription Factor; D015534:Trans-Activators; D000096743:Interferon gamma Receptor; C494079:STAT1 protein, human; C496540:PTGS2 protein, human