Progestin regulates chemokine (C-X-C motif) ligand 14 transcript level in human endometrium
Autor: | Holli Bielby, Norfilza Mohd Mokhtar, D. Stephen Charnock-Jones, Stephen K. Smith, Emma Cook, Ching Wen Cheng |
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Rok vydání: | 2009 |
Předmět: |
Embryology
medicine.medical_specialty Chemokine Gene Expression Electrophoretic Mobility Shift Assay In situ hybridization In Vitro Techniques Biology Response Elements Endometrium Polymerase Chain Reaction Cell Movement Pregnancy Internal medicine Genetics medicine Humans Northern blot Promoter Regions Genetic Receptor CXCL14 Molecular Biology Cells Cultured In Situ Hybridization Menstrual Cycle Progesterone Messenger RNA Obstetrics and Gynecology Chemotaxis Cell Biology Blotting Northern Immunohistochemistry Molecular biology Recombinant Proteins Endocrinology medicine.anatomical_structure Reproductive Medicine Mutagenesis Site-Directed biology.protein Female Progestins Chemokines CXC Developmental Biology |
Zdroj: | Molecular Human Reproduction. 16:170-177 |
ISSN: | 1460-2407 1360-9947 |
DOI: | 10.1093/molehr/gap100 |
Popis: | Leukocyte populations change profoundly in the human endometrium during the menstrual cycle. However the predominant cell, the uterine natural killer (uNK) cell does not contain steroid receptors. From gene array analysis we identified a transcript encoding chemokine (C-X-C motif) ligand 14 (CXCL14) which is markedly up-regulated in the secretory phase of the cycle. We confirm this data by northern blotting and quantitative PCR. Using in situ hybridization we localized CXCL14 mRNA to the glandular epithelial cells where it was detected only in the secretory phase of the cycle. Candidate progesterone response elements were identified at positions -2028/- 2007 and -722/-697 (PRE1 and PRE2, respectively) relative to the translation start site. These were functionally tested using luciferase repor- ter deletion constructs, electrophoretic mobility shift assays and site-directed mutagenesis. The deletion/mutation of these sites reduced progesterone induction by 40 and 20%, respectively. Finally, we demonstrated that recombinant CXCL14 stimulated uNK cell chemotaxis in vitro. We therefore conclude that CXCL14 is likely to be regulated by progesterone in human endometrium and that it may exert a chemoattractive effect on uNK cells and in part be responsible for their clustering around the epithelial glands. |
Databáze: | OpenAIRE |
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