Progesterone induces human leukocyte antigen-g expression in vascular endothelial and smooth muscle cells.

Rohit Sheshgiri, Vivek Rao, Laura C. Tumiati, Rong Xiao, Jessica L. Prodger, Mitesh Badiwala, Clifford Librach, Diego H. Delgado

Research output: Contribution to journalArticle

Abstract

BACKGROUND: Human leukocyte antigen-G (HLA-G) expression in heart transplant patients has been negatively associated with acute cellular rejection and cardiac allograft vasculopathy. We assessed HLA-G expression in vascular human endothelial and smooth muscle cell cultures to determine if future therapeutic agents can be targeted toward inducing HLA-G expression to protect against allograft rejection and vasculopathy. METHODS AND RESULTS: Human coronary artery endothelial, aortic endothelial, and coronary artery smooth muscle cell cultures were exposed to cytokines (interferon-gamma or interleukin-10), hypoxia/reoxygenation stress, immunosuppressive agents (cyclosporine, sirolimus, or tacrolimus), or progesterone. HLA-G was not expressed by untreated, normoxic cells. Furthermore, maximal doses of interferon-gamma, interleukin-10, cyclosporine, sirolimus, or tacrolimus, as well as exposure to hypoxia/reoxygenation, failed to induce HLA-G expression. HLA-G, which has previously not been detected in adult vascular endothelial and smooth muscle cells, was detected by enzyme-linked immunosorbent assay and flow cytometry in human coronary artery endothelial, human coronary aortic endothelial, and human coronary artery smooth muscle cultures after incubation with progesterone in a dose-dependent manner (P<0.001) with no change in cellular proliferation ability or viability. This effect was partially blocked in the presence of mifepristone, a progesterone receptor antagonist (human coronary artery endothelial: 48.8+/-15.6%; human coronary aortic endothelial: 59.5+/-9.5%; human coronary artery smooth muscle: 59.8+/-9.8% of control; P<0.05). Progesterone-induced HLA-G expression was not protective against hypoxia/reoxygenation injury. CONCLUSIONS: HLA-G is not expressed at baseline in vascular endothelial and smooth muscle cells but can be induced by exposure to progesterone. Although tightly regulated, induction of HLA-G expression in these cells may represent a promising and novel therapeutic strategy to protect against rejection and cardiac allograft vasculopathy after heart transplantation.

Original languageEnglish (US)
Pages (from-to)S58-64
JournalCirculation
Volume118
Issue number14 Suppl
DOIs
StatePublished - Sep 30 2008
Externally publishedYes

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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    Sheshgiri, R., Rao, V., Tumiati, L. C., Xiao, R., Prodger, J. L., Badiwala, M., Librach, C., & Delgado, D. H. (2008). Progesterone induces human leukocyte antigen-g expression in vascular endothelial and smooth muscle cells. Circulation, 118(14 Suppl), S58-64. https://doi.org/10.1161/CIRCULATIONAHA.107.757781