Adrenomedullin 2/Intermedin Regulates HLA-G in human trophoblasts

Madhu Chauhan, Meena Balakrishnan, Uma Yallampalli, Janice Endsley, Gary Hankins, Regan Theiler, Chandra Yallampalli

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Adrenomedullin 2 (ADM2), also referred to as intermedin (IMD), is expressed in trophoblast cells in human placenta and enhances the invasion and migration of first-trimester HTR-8SV/ neo cells. Further infusion of ADM2 antagonist in pregnant rat causes fetoplacental growth restriction, suggesting a role for ADM2 in maintaining a successful pregnancy. This study was undertaken to assess whether ADM2 protein is present in decidual tissue and colocalized with HLA-G-positive cytotrophoblast cells and natural killer cells; to assess whether ADM2 regulates expression of HLA-G in trophoblast cells; and to identify whether mitogen-activated protein kinase (MAPK) signaling pathway is involved in ADM2-induced trophoblast cell invasion and migration. Using immunohistochemical methods and RT-PCR, this study shows that ADM2 protein is colocalized with HLA-G-expressing cytotrophoblast cells as well as with NCAM1 (CD56) immunoreactivity in human first-trimester decidual tissue, and that ADM2 mRNA is expressed in peripheral blood natural killer cells. Further, ADM2 dose dependently increases the expression of HLA-G antigen in HTR-8SV/neo cells as well as in term placental villi explants, suggesting involvement of ADM2 in the regulation of HLA-G in trophoblast cells. In addition, interference with the activity of RAF and MAPK3/1 by their inhibitors, manumycin and U0126, respectively, reduces ADM2-induced HTR-8SV/neo cell invasion and migration. In summary, this study suggests a potential involvement for ADM2 in regulating HLA-G antigen at the maternal-fetal interface in human pregnancy and facilitating trophoblast invasion and migration via MAPK3/1 phosphorylation.

Original languageEnglish (US)
Pages (from-to)1232-1239
Number of pages8
JournalBiology of Reproduction
Volume85
Issue number6
DOIs
StatePublished - Dec 1 2011

Fingerprint

HLA-G Antigens
Adrenomedullin
Trophoblasts
First Pregnancy Trimester
Natural Killer Cells
Cell Movement
Chorionic Villi
Pregnancy
Mitogen-Activated Protein Kinases
Placenta

Keywords

  • Early development
  • Early placental development
  • HLA-G
  • MAPK3/1 signaling
  • Placenta
  • Placentation
  • Pregnancy
  • Trophoblast

ASJC Scopus subject areas

  • Cell Biology

Cite this

Chauhan, M., Balakrishnan, M., Yallampalli, U., Endsley, J., Hankins, G., Theiler, R., & Yallampalli, C. (2011). Adrenomedullin 2/Intermedin Regulates HLA-G in human trophoblasts. Biology of Reproduction, 85(6), 1232-1239. https://doi.org/10.1095/biolreprod.110.086835

Adrenomedullin 2/Intermedin Regulates HLA-G in human trophoblasts. / Chauhan, Madhu; Balakrishnan, Meena; Yallampalli, Uma; Endsley, Janice; Hankins, Gary; Theiler, Regan; Yallampalli, Chandra.

In: Biology of Reproduction, Vol. 85, No. 6, 01.12.2011, p. 1232-1239.

Research output: Contribution to journalArticle

Chauhan, M, Balakrishnan, M, Yallampalli, U, Endsley, J, Hankins, G, Theiler, R & Yallampalli, C 2011, 'Adrenomedullin 2/Intermedin Regulates HLA-G in human trophoblasts', Biology of Reproduction, vol. 85, no. 6, pp. 1232-1239. https://doi.org/10.1095/biolreprod.110.086835
Chauhan M, Balakrishnan M, Yallampalli U, Endsley J, Hankins G, Theiler R et al. Adrenomedullin 2/Intermedin Regulates HLA-G in human trophoblasts. Biology of Reproduction. 2011 Dec 1;85(6):1232-1239. https://doi.org/10.1095/biolreprod.110.086835
Chauhan, Madhu ; Balakrishnan, Meena ; Yallampalli, Uma ; Endsley, Janice ; Hankins, Gary ; Theiler, Regan ; Yallampalli, Chandra. / Adrenomedullin 2/Intermedin Regulates HLA-G in human trophoblasts. In: Biology of Reproduction. 2011 ; Vol. 85, No. 6. pp. 1232-1239.
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