NDLI: Uterine NK cells regulate endometrial bleeding in women and are suppressed by the progesterone receptor modulator asoprisnil.

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Uterine NK cells regulate endometrial bleeding in women and are suppressed by the progesterone receptor modulator asoprisnil.

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Uterine NK cells regulate endometrial bleeding in women and are suppressed by the progesterone receptor modulator asoprisnil.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Lourenco, Paula Gibson, Douglas A. Williams, Alistair R. W. Craigon, Marie Critchley, Hilary O. D. Wilkens, Julia Ghazal, Peter Male, Victoria Chwalisz, Kristof Brito-Mutunayagam, Savita L. Moffett, Ashley Forster, Thorsten Cameron, Iain T.
Description	Country affiliation: United kingdom Author Affiliation: Wilkens J ( Medical Research Council Centre for Reproductive Health, University of Edinburgh, Edinburgh EH16 4TJ, United Kingdom.)
Abstract	Uterine NK cells (uNK) play a role in the regulation of placentation, but their functions in nonpregnant endometrium are not understood. We have previously reported suppression of endometrial bleeding and alteration of spiral artery morphology in women exposed to asoprisnil, a progesterone receptor modulator. We now compare global endometrial gene expression in asoprisnil-treated versus control women, and we demonstrate a statistically significant reduction of genes in the IL-15 pathway, known to play a key role in uNK development and function. Suppression of IL-15 by asoprisnil was also observed at mRNA level (p < 0.05), and immunostaining for NK cell marker CD56 revealed a striking reduction of uNK in asoprisnil-treated endometrium (p < 0.001). IL-15 levels in normal endometrium are progesterone-responsive. Progesterone receptor (PR) positive stromal cells transcribe both IL-15 and IL-15RA. Thus, the response of stromal cells to progesterone will be to increase IL-15 trans-presentation to uNK, supporting their expansion and differentiation. In asoprisnil-treated endometrium, there is a marked downregulation of stromal PR expression and virtual absence of uNK. These novel findings indicate that the IL-15 pathway provides a missing link in the complex interplay among endometrial stromal cells, uNK, and spiral arteries affecting physiologic and pathologic endometrial bleeding.
ISSN	00221767
e-ISSN	15506606
DOI	10.4049/jimmunol.1300958
Journal	The Journal of Immunology
Issue Number	5
Volume Number	191
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2013-09-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Estrenes Therapeutic Use Killer Cells, Natural Metabolism Leiomyoma Drug Therapy Oximes Uterine Neoplasms Double-blind Method Endometrium Drug Effects Immunology Immunohistochemistry Interleukin-15 Complications Lymphocyte Activation Oligonucleotide Array Sequence Analysis Receptors, Progesterone Biosynthesis Reverse Transcriptase Polymerase Chain Reaction Transcriptome Uterus Clinical Trial, Phase Ii Multicenter Study Randomized Controlled Trial Research Support, Non-u.s. Gov't Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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