Progestin regulates chemokine (C-X-C motif) ligand 14 transcript level in human endometrium

Norfilza Mohd Mokhtar, Ching Wen Cheng, Emma Cook, Holli Bielby, Stephen K. Smith, D. Stephen Charnock-Jones

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

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 reporter 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.

Original languageEnglish
Article numbergap100
Pages (from-to)170-177
Number of pages8
JournalMolecular Human Reproduction
Volume16
Issue number3
DOIs
Publication statusPublished - 10 Nov 2009

Fingerprint

CXC Chemokines
Progestins
Endometrium
Natural Killer Cells
Ligands
Progesterone
Steroid Receptors
Sequence Deletion
Response Elements
Electrophoretic Mobility Shift Assay
Chemotaxis
Menstrual Cycle
Site-Directed Mutagenesis
Luciferases
Northern Blotting
In Situ Hybridization
Cluster Analysis
Leukocytes
Epithelial Cells
Polymerase Chain Reaction

Keywords

  • CXCL14
  • Endometrium
  • Leukocyte
  • Promoter
  • uNK cell

ASJC Scopus subject areas

  • Molecular Biology
  • Embryology
  • Cell Biology
  • Genetics
  • Developmental Biology
  • Reproductive Medicine
  • Obstetrics and Gynaecology

Cite this

Mohd Mokhtar, N., Cheng, C. W., Cook, E., Bielby, H., Smith, S. K., & Stephen Charnock-Jones, D. (2009). Progestin regulates chemokine (C-X-C motif) ligand 14 transcript level in human endometrium. Molecular Human Reproduction, 16(3), 170-177. [gap100]. https://doi.org/10.1093/molehr/gap100

Progestin regulates chemokine (C-X-C motif) ligand 14 transcript level in human endometrium. / Mohd Mokhtar, Norfilza; Cheng, Ching Wen; Cook, Emma; Bielby, Holli; Smith, Stephen K.; Stephen Charnock-Jones, D.

In: Molecular Human Reproduction, Vol. 16, No. 3, gap100, 10.11.2009, p. 170-177.

Research output: Contribution to journalArticle

Mohd Mokhtar, N, Cheng, CW, Cook, E, Bielby, H, Smith, SK & Stephen Charnock-Jones, D 2009, 'Progestin regulates chemokine (C-X-C motif) ligand 14 transcript level in human endometrium', Molecular Human Reproduction, vol. 16, no. 3, gap100, pp. 170-177. https://doi.org/10.1093/molehr/gap100
Mohd Mokhtar, Norfilza ; Cheng, Ching Wen ; Cook, Emma ; Bielby, Holli ; Smith, Stephen K. ; Stephen Charnock-Jones, D. / Progestin regulates chemokine (C-X-C motif) ligand 14 transcript level in human endometrium. In: Molecular Human Reproduction. 2009 ; Vol. 16, No. 3. pp. 170-177.
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