Angiopoietin-like protein 2 mediates endotoxin-induced acute inflammation in the eye

Abstract

Angiopoietin-like protein (Angptl) 2 is a key mediator linking obesity to chronic adipose-tissue inflammation and systemic insulin resistance, and increasing evidence has shown that Angptl-/-2 is associated with various chronic inflammatory diseases such as cancer and dermatomyositis; however, it remains unclear that Angptl-/-2 functions in acute inflammation. In this study, we investigate whether Angptl-/-2 has a role in acute inflammation in the eye with endotoxin-induced uveitis (EIU). Angptl-/-2 was widely expressed in the normal mouse retina, while Angptl-/-2/mice did not exhibit any changes in retinal cell marker expression and morphological analyses. Treatment with lipopolysaccharide (LPS) stimulated retinal Angptl-/-2 mRNA expression in vivo and in vitro. We generated EIU in wild-type (C57BL/6) and Angptl-/-2/mice by injecting LPS intraperitoneally. Compared with wild-type animals, Angptl -/-2/mice significantly reduced various EIU-associated cellular and molecular parameters including leukocyte adhesion to the retinal vessels and infiltration into the vitreous cavity and retinal mRNA expression levels of monocyte chemotactic protein-1, intercellular adhesion molecule-1, interleukin (IL)-6, and tumor necrosis factor (TNF)-α, together with nuclear translocation of nuclear factor (NF)-κB p65 subunit. In vitro, antibody-based inhibition of α5β1 integrin, a receptor for Angptl-/-2, significantly repressed LPS-induced expression of IL-6 and TNF-α, both of which are the major inflammatory cytokines derived from macrophages. The present findings indicate that Angptl-/-2 mediates endotoxin-induced retinal inflammation through the activation of NF-κB signaling pathway and suggest a potential validity of Angptl-/-2 as a new molecular target for the treatment of acute inflammation. © 2012 USCAP, Inc All rights reserved.