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Mol. Hum. Reprod. Advance Access originally published online on March 8, 2009
Molecular Human Reproduction 2009 15(5):311-319; doi:10.1093/molehr/gap020
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© The Author 2009. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Differential expression and regulation of nuclear oligomerization domain proteins NOD1 and NOD2 in human endometrium: a potential role in innate immune protection and menstruation

Anne E. King1,4, Andrew W. Horne1, Sabine Hombach-Klonisch2,3, J. I. Mason1 and Hilary O.D. Critchley1

1Reproductive and Developmental Sciences, Centre for Reproductive Biology, The Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, UK 2Department of Human Anatomy and Cell Science, University of Manitoba, Winnipeg, Manitoba, Canada 3Department of Obstetrics and Gynecology, University of Manitoba, Winnipeg, Manitoba, Canada

4 Correspondence address. Tel: +44-131-242-6613; Fax: +44-131-242-6441; E-mail: anne.king{at}ed.ac.uk

Nuclear oligomerization domains (NODs) are cytosolic pattern recognition receptors (PRRs), present in epithelial cells, monocytes and dendritic cells. This study details their expression, regulation and role in human endometrium. Real-time PCR showed that NOD1 mRNA is constitutively expressed in endometrium. NOD2 is up-regulated in the late secretory phase of the menstrual cycle suggesting a role in menstruation. Both proteins are immunolocalized in endometrial epithelium, stroma and endothelium. In first trimester, decidua NODs are present in decidualized stroma. NOD function was examined in endometrial stromal cells (ESCs) and endometrial epithelial cells (EEpCs) in vitro. I{kappa}B{alpha} is up-regulated by stimulation of ESC and EEpC with an NOD1 ligand. I{kappa}B{alpha}, IL-8 and TNF{alpha} mRNA expression is increased in EEpC by a NOD2 ligand. NOD2 mRNA expression increases in response to IL-1 treatment while NOD1 transcripts are unaltered. NOD1 mRNA is increased in an in vitro model of decidualization of ESC. In summary, we report expression of NOD1 and NOD2 in human endometrium and show that they are differentially regulated. NOD2 and, to a lesser extent, NOD1 can function to increase expression of innate immune molecules in endometrium. NODs may have a role in innate immune protection in the uterus and NOD2 may regulate inflammation associated with menstruation.

Key words: endometrium/implantation/innate immunity/menstruation/NODs

Submitted on November 27, 2008; resubmitted on March 4, 2009; accepted on March 5, 2009.


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