期刊
JOURNAL OF REPRODUCTIVE IMMUNOLOGY
卷 99, 期 1-2, 页码 24-32出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.jri.2013.04.005
关键词
Myometrium; Labour; FOXO1; Inflammation; Cytokines; Prostaglandins
资金
- National Health and Medical Research Council (NHMRC) [1047025]
- Medical Research Foundation for Women and Babies
Prematurity is the most important complication contributing to neonatal morbidity and mortality. It is the untimely activation of the terminal events of human parturition that lead to preterm birth, with inflammation playing a driving role in initiating uterine contractions. The purpose of this study was to investigate the role of Forkhead box 01 (FOXO1), a pro-inflammatory modulator, during human parturition. FOXO1 mRNA expression was quantified using qRT-PCR, and protein expression using Western blotting in myometrial biopsies from pregnant non-labouring and labouring women at term. In addition, the effect of FOXO1 knockdown in human myometrial cells on IL-beta-stimulated expression of pro-inflammatory mediators was investigated. Levels of FOXO1, at both the gene and protein levels, were higher in myometrium obtained from women in labour compared With samples taken from non-labouring women. FOXO1 deletion in myometrial cells attenuated the capacity of IL-1 beta to induce inflammatory gene expression. Specifically, FOXO1 knockdown significantly decreased IL-1 beta-induced IL-6 and IL-8 expression; production and COX-2 expression and subsequent prostaglandin (PGE(2) and PGF(2 alpha)) release; and MMP-9 mRNA expression and activity. In summary, this study demonstrates for the first time the potential role of FOXO1 inflammatory events of both physiological and pathological labour in human myometrium, and may provide a therapeutic target in the management of preterm labour. (C) 2013 Elsevier Ireland Ltd. All rights reserved.
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