RT info:eu-repo/semantics/article
T1 Topical application of TGF-β-activating peptide, KRFK, prevents inflammatory manifestations in the TSP-1-deficient mouse model of chronic ocular inflammation
A1 Soriano Romaní, Laura
A1 Contreras Ruiz, Laura
A1 López García, Antonio
A1 Diebold Luque, María Yolanda
A1 Masli, Sharmila
K1 Inflammation
K1 KRFK peptide
K1 Ocular surface
K1 Thrombospondin-1
K1 Transforming growth factor-β
K1 32 Ciencias Médicas
AB Chronic inflammation of the ocular surface poses a risk of vision impairment. The understanding of the molecular mechanisms that are involved in the inflammatory response is critical to identify novel molecular targets. Recently, thrombospondin-1 (TSP-1) has emerged as a key player in ocular surface homeostasis that efficiently activates the TGF-β2 isoform that is predominantly expressed in the ocular mucosa. Here, the potential of the peptide derived from TSP-1 (KRFK), that can activate TGF-β, is proposed as a potentially applicable therapeutic for chronic ocular surface inflammatory disorders. Our in vitro results confirm that the chosen peptide activates TGF-β, reducing the expression of co-stimulatory molecules on dendritic cells, driving them towards a tolerogenic phenotype. For the in vivo studies, the TSP-1−/− mouse is used as a pre-clinical model of chronic ocular inflammation. We observe that the topical application of KRFK alters the peripheral balance of effectors by reducing the proportion of pathogenic Th1 and Th17 cells while increasing Treg cell proportion in cervical lymph nodes. In line with these findings, the development of chronic ocular surface inflammation is significantly prevented in KRFK-treated TSP-1−/− mice, as assessed by clinical parameters and inflammatory cytokine expression in conjunctival and lacrimal gland tissues. Together, our results identify the KRFK peptide as a novel therapeutic option to prevent the development of chronic inflammatory manifestations of the ocular surface.
PB MDPI
SN 1661-6596
YR 2019
FD 2019
LK https://uvadoc.uva.es/handle/10324/52280
UL https://uvadoc.uva.es/handle/10324/52280
LA eng
NO International Journal of Molecular Sciences,  2019, vol. 20, n. 1, p. 9.
NO Producción Científica
DS UVaDOC
RD 11-jul-2024