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Corticotropin-releasing hormone intereacts with interleukin-1 beta to regulate prostaglandin H synthase-2 expression in human myometrium during pregnancy and labor
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Markovic, Danijela, Bari, Muhammad F., Lu, Buyu, Vatish, Manu and Grammatopoulos, Dimitris (2013) Corticotropin-releasing hormone intereacts with interleukin-1 beta to regulate prostaglandin H synthase-2 expression in human myometrium during pregnancy and labor. Journal of Clinical Endocrinology & Metabolism , 98 (7). pp. 2864-2875.
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Official URL: http://dx.doi.org/10.1210/jc.2013-1094
Abstract
Context:
The onset of labor appears to involve the activation of myometrial inflammatory pathways, and transcription factors such as nuclear factor-κB (NF-κB) control expression of the contraction-associated proteins required to induce a procontractile phenotype. These responses might involve CRH, which integrates immune and neuroendocrine systems.
Objectives:
In human myometrium we investigated cyclooxygenase 2 (PGHS2) expression and regulation by CRH and the proinflammatory cytokine IL-1β before and after labor.
Design:
Myometrial tissues obtained from pregnant women at term before (n = 12) or during labor (n = 10) and pathological cases of choriamnionitis-associated term labor (n = 5) were used to isolate primary myocytes and investigate in vitro, CRH effects on basal and IL-1β regulated p65 activation and PGHS2 expression.
Results:
In nonlaboring myometrial cells, CRH was unable to induce NF-κB nuclear translocation; however, it altered the temporal dynamics of IL-1β-driven NF-κB nuclear entry by initially delaying entry and subsequently prolonging retention. These CRH-R1-driven effects were associated with a modest inhibitory action in the early phase (within 2 hours) of IL-1β stimulated PGHS2 mRNA expression, whereas prolonged stimulation for 6-18 hours augmented the IL-1β effects. The early-phase effect required intact protein kinase A activity and was diminished after the onset of labor. The presence of chorioamnionitis led to exaggerated PGHS2 mRNA responses to IL-1β but diminished effects of CRH.
Conclusions:
CRH is involved in the inflammatory regulation of PGHS2 expression before and during labor; these actions might be important in priming and preparing the myometrium for labor and cellular adaptive responses to inflammatory mediators.
| Item Type: | Journal Article | ||||||||||
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| Subjects: | R Medicine > RC Internal medicine | ||||||||||
| Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine > Metabolic and Vascular Health (- until July 2016) Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
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| Library of Congress Subject Headings (LCSH): | Myometrium, Pregnancy -- Complications | ||||||||||
| Journal or Publication Title: | Journal of Clinical Endocrinology & Metabolism | ||||||||||
| Publisher: | Endocrine Society | ||||||||||
| ISSN: | 0021-972x | ||||||||||
| Official Date: | July 2013 | ||||||||||
| Dates: |
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| Volume: | 98 | ||||||||||
| Number: | 7 | ||||||||||
| Number of Pages: | 12 | ||||||||||
| Page Range: | pp. 2864-2875 | ||||||||||
| Status: | Peer Reviewed | ||||||||||
| Publication Status: | Published | ||||||||||
| Access rights to Published version: | Open Access | ||||||||||
| Funder: | Wellcome Trust (London, England), Birmingham Science City |
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