2026-05-05T20:55:27Zhttps://uvadoc.uva.es/oai/requestoai:uvadoc.uva.es:10324/617422025-02-19T12:04:18Zcom_10324_40357com_10324_952com_10324_894col_10324_40358
2023-09-21T12:39:24Z
urn:hdl:10324/61742
CD47 binding on vascular endothelial cells inhibits IL-17-mediated leukocyte adhesion
Soriano Romani, Laura
Mir, Fayaz A.
Singh, Niharika
Chin, Ian
Hafezi Moghadam, Ali
Masli, Sharmila
Inflammation
Inflamación
Eye - Diseases
Ojos - Enfermedades
Ojo - Inflamación
Chronic inflammation
Leucocytes
Endothelial cells
Endotelio vascular
Cell Biology
Cell adhesion
Ophthalmology
Producción Científica
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.
2023-09-21T12:39:24Z
2023-09-21T12:39:24Z
2022
info:eu-repo/semantics/article
International Journal of Molecular Sciences, 2022, Vol. 23, Nº. 10, 5705
1422-0067
https://uvadoc.uva.es/handle/10324/61742
10.3390/ijms23105705
5705
10
International Journal of Molecular Sciences
23
1422-0067
eng
https://www.mdpi.com/1422-0067/23/10/5705
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/4.0/
© 2022 The Authors
Atribución 4.0 Internacional
MDPI