Prevention of inflammatory activation of human gestational membranes in an ex vivo model using a pharmacological NF-κB inhibitor

Keelan, Jeffrey A., Khan, Sadiqa, Yosaatmadja, Francisca and Mitchell, Murray A. (2009) Prevention of inflammatory activation of human gestational membranes in an ex vivo model using a pharmacological NF-κB inhibitor. Journal of Immunology, 183 8: 5270-5278. doi:10.4049/jimmunol.0802660


Author Keelan, Jeffrey A.
Khan, Sadiqa
Yosaatmadja, Francisca
Mitchell, Murray A.
Title Prevention of inflammatory activation of human gestational membranes in an ex vivo model using a pharmacological NF-κB inhibitor
Journal name Journal of Immunology   Check publisher's open access policy
ISSN 0022-1767
1550-6606
Publication date 2009-10-15
Sub-type Article (original research)
DOI 10.4049/jimmunol.0802660
Volume 183
Issue 8
Start page 5270
End page 5278
Total pages 9
Place of publication Bethesda, MD, United States
Publisher American Association of Immunologists
Language eng
Abstract Intrauterine inflammation plays a major role in the etiology of preterm labor and birth. We established an ex vivo model employing perfused full-thickness term gestational membranes to study membrane transport, function, and inflammatory responses. Exposure of the maternal (decidual) face of the membranes to LPS (5 μg/ml) resulted in increased accumulation of proinflammatory cytokines in the maternal compartment within 4 h, followed by a response in the fetal (amniotic) compartment. Using cytokine arrays, exposure to LPS was found to result in increased secretion of a large number of cytokines and chemokines in both compartments, most notably IL-5, IL-6, IL-7, MDC (macrophage-derived chemokine), MIG (monokine induced by IFN-γ), TARC (thymus and activation-regulated chemokine), TGF-β, and TNF-α. PGE2 accumulation also increased in response to LPS, particularly in the fetal compartment. Cotreatment with sulfasalazine, which inhibited nuclear translocation of NF-κB p65, had a rapid and marked inhibitory effect on the rate of cytokine accumulation in the maternal compartment, with lesser but significant effects observed in the fetal compartment. While membrane integrity was not discernibly impaired with LPS or sulfasalazine exposure, rates of chorionic apoptosis after 20 h were doubled in sulfasalazine-treated tissues. We conclude that the system described provides a means of accurately modeling human gestational membrane functions and inflammatory activation ex vivo. Decidual LPS exposure was shown to elicit a robust inflammatory response in both the maternal and fetal compartments. Sulfasalazine was an effective antiinflammatory agent in this model, but also exerted proapoptotic effects that raise concerns regarding its placental effects when administered in pregnancy.
Keyword Human-Fetal Membranes
Bowel-Disease
Preterm Birth
15-Hydroxyprostaglandin Dehydrogenase
Proinflammatory Cytokines
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: UQ Centre for Clinical Research Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 27 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 27 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Tue, 19 Jul 2011, 23:19:03 EST by System User on behalf of UQ Centre for Clinical Research