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

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Show simple item record Keelan, JA en Khan, S en Yosaatmadja, F en Mitchell, Murray en 2012-05-30T03:06:46Z en 2009 en
dc.identifier.citation Journal of Immunology 183(8):5270-5278 2009 en
dc.identifier.issn 1550-6606 en
dc.identifier.uri en
dc.description.abstract 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 g/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- ), TARC (thymus and activation-regulated chemokine), TGF- , and TNF- . PGE2 accumulation also increased in response to LPS, particularly in the fetal compartment. Cotreatment with sulfasalazine, which inhibited nuclear translocation of NF- B 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 en
dc.publisher Williams & Wilkins en
dc.relation.ispartofseries Journal of Immunology en
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. Details obtained from en
dc.rights.uri en
dc.title Prevention of inflammatory activation of human gestational membranes in an ex vivo model using a pharmacological NF-kappaB inhibitor en
dc.type Journal Article en
dc.identifier.doi 10.4049/jimmunol.0802660 en
pubs.issue 8 en
pubs.begin-page 5270 en
pubs.volume 183 en
dc.rights.holder Copyright: Williams & Wilkins en
dc.identifier.pmid 19783681 en
pubs.end-page 5278 en
dc.rights.accessrights en
pubs.subtype Article en
pubs.elements-id 100239 en
pubs.record-created-at-source-date 2010-09-01 en
pubs.dimensions-id 19783681 en

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