Αρχειοθήκη ιστολογίου

Αλέξανδρος Γ. Σφακιανάκης
ΩτοΡινοΛαρυγγολόγος
Αναπαύσεως 5
Άγιος Νικόλαος Κρήτη 72100
2841026182
6032607174

Τρίτη 2 Οκτωβρίου 2018

Netrin-1 prevents the attachment of monocytes to endothelial cells via an anti-inflammatory effect

Publication date: November 2018

Source: Molecular Immunology, Volume 103

Author(s): Zhaoheng Lin, Jing Jin, Weirong Bai, Jiao Li, Xiyun Shan

Abstract

Netrin-1 is best known for its function guiding axon growth and migration. Netrin-1 has been shown to be involved in regulating cardiovascular function. In this study, we aimed to understand the biological role of Netrin-1 and its receptor Unc5b in endothelial cells. Our results demonstrate that Unc5b was moderately expressed in human aortic endothelial cells (HAECs) and TNF-α had a dose-dependent inhibitory effect on Unc5b level. Netrin-1 potently suppressed TNF-α-induced vascular adhesion molecules VCAM-1, ICAM-1, E-selectin and blocked the adhesion of monocytes to endothelial cells. Netrin-1 also suppressed TNF-α-induced production of cytokines including MCP-1, IL-1β, and IL-6. Importantly, Netrin-1 suppressed toll like receptor 4 (TLR4) expression and prevented NF-κB activation. Mechanistically, Netrin-1 reduced TNF-α-induced IKK and IκBα activation and prevented degradation of IκBα. Netrin-1 reduced nuclear accumulation of p65 and strongly suppressed NF-κB promoter activation. Collectively, our data demonstrated that signaling of Netrin-1 and its receptor Unc5b had an anti-inflammatory effect in endothelial cells. Netrin-1 signaling could be imperative for normal endothelial function.



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