NF-kB regulates a cassette of immune/inflammatory genes in human pregnant myometrium at term

Title: NF-kB regulates a cassette of immune/inflammatory genes in human pregnant myometrium at term
Authors: Khanjani, S
Kandola, MK
Lindstrom, TM
Sooranna, SR
Melchionda, M
Lee, YS
Terzidou, V
Johnson, MR
Bennett, PR
Item 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.
Issue Date: 7-Apr-2010
Date of Acceptance: 19-Mar-2010
URI: http://hdl.handle.net/10044/1/43508
DOI: https://dx.doi.org/10.1111/j.1582-4934.2010.01069.x
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/)
Keywords: 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
NF-kappa B
Oligonucleotide Array Sequence Analysis
Phosphorylation
Pregnancy
Protein Binding
Protein Transport
Reproducibility of Results
Transcription Factor RelA
Myometrium
Cell Nucleus
Humans
Inflammation
NF-kappa B
DNA
Oligonucleotide Array Sequence Analysis
Reproducibility of Results
Gene Expression Profiling
Gene Expression Regulation
Protein Binding
Protein Transport
Phosphorylation
Pregnancy
Labor, Obstetric
Female
I-kappa B Proteins
Transcription Factor RelA
Interleukin-1beta
Biochemistry & Molecular Biology
0304 Medicinal And Biomolecular Chemistry
0601 Biochemistry And Cell Biology
1103 Clinical Sciences
Publication Status: Published
Appears in Collections:Division of Surgery
Faculty of Medicine



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