CD47 Binding on Vascular Endothelial Cells Inhibits IL-17-Mediated Leukocyte Adhesion.

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  • Additional Information
    • Source:
      Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE
    • Publication Information:
      Original Publication: Basel, Switzerland : MDPI, [2000-
    • Subject Terms:
      CD47 Antigen*/genetics ; CD47 Antigen*/metabolism ; Cell Adhesion* ; Endothelial Cells*/metabolism ; Leukocytes*/metabolism ; Thrombospondin 1*/metabolism; Animals ; Interleukin-17/metabolism ; Mice ; Vascular Cell Adhesion Molecule-1/genetics ; Vascular Cell Adhesion Molecule-1/metabolism
    • Abstract:
      To address the conflicting role of thrombospondin (TSP)-1 reported in acute and chronic pathologies, this study investigated the role of TSP-1 in regulating leukocyte recruitment and regulation of VCAM-1 expression using mouse models of uveitis. The spontaneously increased VCAM-1 expression and leukocyte adhesion in retinas of TSP-1-deficient mice suggested a TSP-1-mediated regulation of VCAM-1 expression. In a chronic uveitis model, induced by immunizing wild-type mice with specific interphotoreceptor retinoid-binding protein (IRBP) peptide, topically applied TSP-1-derived CD47-binding peptide significantly reduced the clinical disease course and retinal leukocyte adhesion as compared to the control peptide-treated group. In contrast, in LPS-mediated acute uveitis, TSP-1 deficiency significantly reduced the retinal leukocyte adhesion. The results of our in vitro study, using vascular endothelial cell (EC) cultures, demonstrate that unlike TNF-α, VCAM-1 expression induced by IL-17 is associated with a reduced expression of endogenous TSP-1. Such reduced endogenous TSP-1 expression in IL-17-stimulated ECs helps limit the CD36-mediated increased VCAM-1 expression, while favoring CD47-mediated inhibition of VCAM-1 expression and leukocyte adhesion. Thus, our study identifies TSP-1:CD47 interaction as a molecular pathway that modulates IL-17-mediated VCAM-1 expression, contributing to its anti-inflammatory effect in chronic inflammatory conditions.
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    • Grant Information:
      DP3 DK108238 United States DK NIDDK NIH HHS; R01 EY015472 United States EY NEI NIH HHS; EY015472 United States NH NIH HHS
    • Contributed Indexing:
      Keywords: CD47; VCAM-1; chronic ocular inflammation; leukocyte adhesion; vascular endothelial cells
    • Accession Number:
      0 (CD47 Antigen)
      0 (Cd47 protein, mouse)
      0 (Interleukin-17)
      0 (Thrombospondin 1)
      0 (Vascular Cell Adhesion Molecule-1)
    • Publication Date:
      Date Created: 20220528 Date Completed: 20220531 Latest Revision: 20240923
    • Publication Date:
      20240923
    • Accession Number:
      PMC9146020
    • Accession Number:
      10.3390/ijms23105705
    • Accession Number:
      35628515