A novel function for programmed death ligand-1 regulation of angiogenesis

Yiping Jin, Sunil K. Chauhan, Jaafar El-Annan, Peter T. Sage, Arlene H. Sharpe, Reza Dana

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Programmed death ligand-1 (PD-L1) plays a critical role in T-cell regulatory function. Here, we report a newly discovered effect of PD-L1 on angiogenesis. We demonstrate that PD-L1 and its receptor CD80, but not PD-1, are expressed by primary murine lung and heart vascular endothelial cells and the miscrovascular endothelial cell line (MS1) at both the mRNA and protein levels in vitro. The inhibition of PD-L1 or CD80 expression in MS1 cells, by small-interfering RNA transfection, led to a significant up-regulation of vascular endothelial growth factor receptor 2 expression and cell proliferation levels in MS1 cells. Furthermore, MS1 cells were found to have a significantly lower proliferation and vascular endothelial growth factor receptor 2 expression levels when they were co-cultured with PD-L1 - expressing normal corneal epithelial cells, as compared to MS1 cells co-cultured with PD-L1-/- corneal epithelial cells. In a suture-induced corneal angiogenesis model, we observed a significantly higher level of angiogenic response in PD-L1 -/- knockout mice as compared to wild-type mice, although there was no significant difference in the expression of inflammatory cytokines (interleukin-1α, interleukin-1β, or tumor necrosis factor-α) or the infiltration of innate immune cells (neutrophils and macrophages) between the two groups. We conclude that the expression of PD-L1 in both vascular endothelial cells and corneal epithelial cells regulates corneal angiogenesis.

Original languageEnglish (US)
Pages (from-to)1922-1929
Number of pages8
JournalAmerican Journal of Pathology
Volume178
Issue number4
DOIs
StatePublished - Apr 2011
Externally publishedYes

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Ligands
Corneal Neovascularization
Vascular Endothelial Growth Factor Receptor-2
Endothelial Cells
Epithelial Cells
Interleukin-1
Regulatory T-Lymphocytes
Knockout Mice
Sutures
Small Interfering RNA
Transfection
Cultured Cells
Neutrophils
Up-Regulation
Tumor Necrosis Factor-alpha
Macrophages
Cell Proliferation
Cytokines
Cell Line
Lung

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

A novel function for programmed death ligand-1 regulation of angiogenesis. / Jin, Yiping; Chauhan, Sunil K.; El-Annan, Jaafar; Sage, Peter T.; Sharpe, Arlene H.; Dana, Reza.

In: American Journal of Pathology, Vol. 178, No. 4, 04.2011, p. 1922-1929.

Research output: Contribution to journalArticle

Jin, Yiping ; Chauhan, Sunil K. ; El-Annan, Jaafar ; Sage, Peter T. ; Sharpe, Arlene H. ; Dana, Reza. / A novel function for programmed death ligand-1 regulation of angiogenesis. In: American Journal of Pathology. 2011 ; Vol. 178, No. 4. pp. 1922-1929.
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