RT info:eu-repo/semantics/article
T1 CD47 binding on vascular endothelial cells inhibits IL-17-mediated leukocyte adhesion
A1 Soriano Romaní, Laura
A1 Mir, Fayaz A.
A1 Singh, Niharika
A1 Chin, Ian
A1 Hafezi Moghadam, Ali
A1 Masli, Sharmila
K1 Inflammation
K1 Inflamación
K1 Eye - Diseases
K1 Ojos - Enfermedades
K1 Ojo - Inflamación
K1 Chronic inflammation
K1 Leucocytes
K1 Endothelial cells
K1 Endotelio vascular
K1 Cell Biology
K1 Cell adhesion
K1 Ophthalmology
K1 3201.09 Oftalmología
K1 2407 Biología Celular
AB 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.
PB MDPI
SN 1422-0067
YR 2022
FD 2022
LK https://uvadoc.uva.es/handle/10324/61742
UL https://uvadoc.uva.es/handle/10324/61742
LA eng
NO International Journal of Molecular Sciences, 2022, Vol. 23, Nº. 10, 5705
NO Producción Científica
DS UVaDOC
RD 24-nov-2024