IL-6 Trans-Signaling System in Intra-Amniotic Inflammation, Preterm Birth, and Preterm Premature Rupture of the Membranes
| Autor: | Mert Ozan Bahtiyar, Sarah Y. Lee, Stephen F. Thung, Unzila Ali, Irina A. Buhimschi, Antonette T. Dulay, Edmund F. Funai, Guomao Zhao, Sonya S. Abdel-Razeq, Catalin S. Buhimschi |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Adult
Fetal Membranes Premature Rupture medicine.medical_specialty Amniotic fluid Immunology Inflammation Matrix Metalloproteinase Inhibitors Biology Article Young Adult Pregnancy Placenta Internal medicine Cytokine Receptor gp130 medicine Humans Immunology and Allergy Receptor Fetus Interleukin-6 Infant Newborn Gestational age Amniotic Fluid medicine.disease Receptors Interleukin-6 female genital diseases and pregnancy complications Pregnancy Complications medicine.anatomical_structure Endocrinology Matrix Metalloproteinase 9 Amniocentesis Premature Birth Female Inflammation Mediators medicine.symptom Premature rupture of membranes Infant Premature Ex vivo Signal Transduction |
| Zdroj: | The Journal of Immunology. 186:3226-3236 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.1003587 |
| Popis: | Classic IL-6 signaling is conditioned by the transmembrane receptor (IL-6R) and homodimerization of gp130. During trans-signaling, IL-6 binds to soluble IL-6R (sIL-6R), enabling activation of cells expressing solely gp130. Soluble gp130 (sgp130) selectively inhibits IL-6 trans-signaling. To characterize amniotic fluid (AF) IL-6 trans-signaling molecules (IL-6, sIL-6R, sgp130) in normal gestations and pregnancies complicated by intra-amniotic inflammation (IAI), we studied 301 women during second trimester (n = 39), third trimester (n = 40), and preterm labor with intact (n = 131, 85 negative IAI and 46 positive IAI) or preterm premature rupture of membranes (PPROM; n = 91, 61 negative IAI and 30 positive IAI). ELISA, Western blotting, and real-time RT-PCR were used to investigate AF, placenta, and amniochorion for protein and mRNA expression of sIL-6R, sgp130, IL-6R, and gp130. Tissues were immunostained for IL-6R, gp130, CD15+ (polymorphonuclear), and CD3+ (T cell) inflammatory cells. The ability of sIL-6R and sgp130 to modulate basal and LPS-stimulated release of amniochorion matrix metalloprotease-9 was tested ex vivo. We showed that in physiologic gestations, AF sgp130 decreases toward term. AF IL-6 and sIL-6R were increased in IAI, whereas sgp130 was decreased in PPROM. Our results suggested that fetal membranes are the probable source of AF sIL-6R and sgp130. Immunohistochemistry and RT-PCR revealed increased IL-6R and decreased gp130 expression in amniochorion of women with IAI. Ex vivo, sIL-6R and LPS augmented amniochorion matrix metalloprotease-9 release, whereas sgp130 opposed this effect. We conclude that IL-6 trans-signaling molecules are physiologic constituents of the AF regulated by gestational age and inflammation. PPROM likely involves functional loss of sgp130. |
| Databáze: | OpenAIRE |
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