2026-05-05T12:32:24Zhttps://uvadoc.uva.es/oai/request

oai:uvadoc.uva.es:10324/617422025-02-19T12:04:18Zcom_10324_40357com_10324_952com_10324_894col_10324_40358

Soriano Romani, Laura Mir, Fayaz A. Singh, Niharika Chin, Ian Hafezi Moghadam, Ali Masli, Sharmila 2022 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. application/pdf https://uvadoc.uva.es/handle/10324/61742 eng MDPI Inflammation Inflamación Eye - Diseases Ojos - Enfermedades Ojo - Inflamación Chronic inflammation Leucocytes Endothelial cells Endotelio vascular Cell Biology Cell adhesion Ophthalmology 3201.09 Oftalmología 2407 Biología Celular CD47 binding on vascular endothelial cells inhibits IL-17-mediated leukocyte adhesion info:eu-repo/semantics/article TEXT UVaDOC. Repositorio Documental de la Universidad de Valladolid Hispana