title: NF-κB regulates a cassette of immune/inflammatory genes in human pregnant myometrium at term.
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.
authors.affiliation: Parturition Research Group, Imperial College London, Institute of Reproductive and Developmental Biology, London, UK. S.Khanjani@imperial.ac.uk
authors.forename: Shirin
authors.initials: S
authors.lastname: Khanjani
authors.forename: Mandeep K
authors.initials: MK
authors.lastname: Kandola
authors.forename: Tamsin M
authors.initials: TM
authors.lastname: Lindstrom
authors.forename: Suren R
authors.initials: SR
authors.lastname: Sooranna
authors.forename: Manuela
authors.initials: M
authors.lastname: Melchionda
authors.forename: Yun S
authors.initials: YS
authors.lastname: Lee
authors.forename: Vasso
authors.initials: V
authors.lastname: Terzidou
authors.forename: Mark R
authors.initials: MR
authors.lastname: Johnson
authors.forename: Phillip R
authors.initials: PR
authors.lastname: Bennett
mesh_terms: D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D020672:I-kappa B Proteins / Q000235:genetics / Q000378:metabolism; D007249:Inflammation / Q000235:genetics* / Q000276:immunology*; D053583:Interleukin-1beta / Q000494:pharmacology; D007743:Labor, Obstetric / Q000187:drug effects / Q000235:genetics; D009215:Myometrium / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D010766:Phosphorylation / Q000187:drug effects; D011247:Pregnancy; D011485:Protein Binding / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D015203:Reproducibility of Results; D051996:Transcription Factor RelA / Q000235:genetics / Q000378:metabolism
chemical_list: D020672:I-kappa B Proteins; D053583:Interleukin-1beta; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D051996:Transcription Factor RelA; D000072000:NF-KappaB Inhibitor alpha; D004247:DNA
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