NF-kB regulates a cassette of immune/inflammatory genes in human pregnant myometrium at term
Author(s)
Type
Journal Article
Abstract
The onset of human labour resembles inflammation with increased synthesis of prostaglandins and cytokines. There is evidence from rodent models for an important role for nuclear factor-κB (NF-κB) activity in myometrium which both up-regulates contraction-associated proteins and antagonizes the relaxatory effects of progesterone. Here we show that in the human, although there are no differences in expression of NF-κB p65, or IκB-α between upper- or lower-segment myometrium or before or after labour, there is nuclear localization of serine-256-phospho-p65 and serine-536-phospho-p65 in both upper- and lower-segment myometrium both before and after the onset of labour at term. This shows that NF-κB is active in both upper and lower segment prior to the onset of labour at term. To identify the range of genes regulated by NF-κB we overexpressed p65 in myocytes in culture. This led to NF-κB activation identical to that seen following interleukin (IL)-1β stimulation, including phosphorylation and nuclear translocation of p65 and p50. cDNA microarray analysis showed that NF-κB increased expression of 38 genes principally related to immunity and inflammation. IL-1β stimulation also resulted in an increase in the expression of the same genes. Transfection with siRNA against p65 abolished the response to IL-1β proving a central role for NF-κB. We conclude that NF-κB is active in myocytes in both the upper and lower segment of the uterus prior to the onset of labour at term and principally regulates a group of immune/inflammation associated genes, demonstrating that myocytes can act as immune as well as contractile cells.
Date Issued
2010-04-07
Date Acceptance
2010-03-19
Citation
Journal of Cellular and Molecular Medicine, 2010, 15 (4), pp.809-824
ISSN
1582-4934
Publisher
Wiley
Start Page
809
End Page
824
Journal / Book Title
Journal of Cellular and Molecular Medicine
Volume
15
Issue
4
Copyright Statement
© 2011 The Authors Journal of Cellular and Molecular Medicine © 2011 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd. This is an Open Access article published under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/3.0/)
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000290312700010&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
Science & Technology
Life Sciences & Biomedicine
Cell Biology
Medicine, Research & Experimental
Research & Experimental Medicine
CELL BIOLOGY
MEDICINE, RESEARCH & EXPERIMENTAL
labour
myometrium
NF-kappa B
cytokines
chemokines
AMNIOTIC-FLUID INTERLEUKIN-6
HUMAN OXYTOCIN RECEPTOR
HUMAN UTERINE MYOCYTES
HUMAN FETAL MEMBRANES
PRETERM LABOR
GESTATIONAL-AGE
UP-REGULATION
CHEMOKINE CCL20
IMMUNE-RESPONSE
RAT MYOMETRIUM
Cell Nucleus
DNA
Female
Gene Expression Profiling
Gene Expression Regulation
Humans
I-kappa B Proteins
Inflammation
Interleukin-1beta
Labor, Obstetric
Myometrium
NF-KappaB Inhibitor alpha
Oligonucleotide Array Sequence Analysis
Phosphorylation
Pregnancy
Protein Binding
Protein Transport
Reproducibility of Results
Transcription Factor RelA
Biochemistry & Molecular Biology
0304 Medicinal And Biomolecular Chemistry
0601 Biochemistry And Cell Biology
1103 Clinical Sciences
Publication Status
Published