Nuclear factor-kappa B localization and function within intrauterine tissues from term and preterm labor and cultured fe
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RESEARCH
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Nuclear factor-kappa B localization and function within intrauterine tissues from term and preterm labor and cultured fetal membranes Sonali Vora1, Asad Abbas2, Chong J Kim2,3,4, Taryn LS Summerfield1,5, Juan P Kusanovic2,3, Jay D Iams5, Roberto Romero2,3, Douglas A Kniss1,5,6, William E Ackerman IV1,5*
Abstract Background: The objective of this study was to quantify the nuclear localization and DNA binding activity of p65, the major transactivating nuclear factor-kappa B (NF-kappaB) subunit, in full-thickness fetal membranes (FM) and myometrium in the absence or presence of term or preterm labor. Methods: Paired full-thickness FM and myometrial samples were collected from women in the following cohorts: preterm no labor (PNL, N = 22), spontaneous preterm labor (PTL, N = 21), term no labor (TNL, N = 23), and spontaneous term labor (STL, N = 21). NF-kappaB p65 localization was assessed by immunohistochemistry, and DNA binding activity was evaluated using an enzyme-linked immunosorbent assay (ELISA)-based method. Results: Nuclear p65 labeling was rare in amnion and chorion, irrespective of clinical context. In decidua, nuclear p65 labeling was greater in the STL group relative to the TNL cohort, but there were no differences among the TNL, PTL, and PNL cohorts. In myometrium, diffuse p65 nuclear labeling was significantly associated with both term and preterm labor. There were no significant differences in ELISA-based p65 binding activity in amnion, choriodecidual, and myometrial specimens in the absence or presence of term labor. However, parallel experiments using cultured term fetal membranes demonstrated high levels of p65-like binding even the absence of cytokine stimulation, suggesting that this assay may be of limited value when applied to tissue specimens. Conclusions: These results suggest that the decidua is an important site of NF-kappaB regulation in fetal membranes, and that mechanisms other than cytoplasmic sequestration may limit NF-kappaB activation prior to term.
Background The precise molecular mechanisms that underpin the commencement of cervical effacement and dilatation, and robust, synchronous myometrial contractions resulting in expulsion of the fetus at term are still incompletely understood. Moreover, the untimely onset of labor prior to 37 weeks of gestation currently contributes to a 12.5% rate of preterm deliveries culminating in significant perinatal morbidity and mortality [1]. This actually represents a substantial increase over estimates from just a decade ago.
* Correspondence: [email protected] 1 Laboratory of Perinatal Research, Department of Obstetrics & Gynecology, College of Medicine, The Ohio State University, Columbus, OH, USA
Despite the rather dismal epidemiological picture, there is now a nearly complete consensus that spontaneous preterm labor is initiated by a complex set of biochemical events that can be categorized as localized inflammation resulting from the untimely activation of the innate immune response within the intrauterine microenvir
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