Involvement of TGF-β in IL-37 induced angiogenesis

• 1、Medcine school of Tongji university

Abstract：Interleukin -37 (IL-37) is an anti-inflammatory cytokine of the IL-1 family and is upregulated in many angiogenesis related diseases. Our previous study found that IL-37 potently promotes endothelial cell activation and pathological angiogenesis. We find that IL-37 binds with ALK-1, a receptor of TGF-β which promotes angiogenesis. However, the mechanisms underlying the pro-angiogenic effects of IL-37 are poorly understood. Based on our previous studies, we investigated the molecular mechanism by which IL-37 promotes angiogenesis using models of in vitro model of tube formation, ex vivo model of aortic ring assay and in vivo models such as mice retinal vascular development, Matrigel plug and oxygen induced retinopathy. We found that TGF-β and ALK1 are both essential for IL-37-induced pro-angiogenic responses. In vitro, blocking the TGF-β/ALK-1 signaling by neutralizing antibodies or shRNA significantly inhibited IL-37-induced endothelial cell activation. Ex vivo, TGF-β neutralizing antibody and ALK-1 inhibitor significantly reduced IL-37-induced vascular sprouting and tube formation. In vivo, blocking TGF-β or ALK-1 results in a significantly reduce of IL-37-induced angiogenesis. The result suggests that IL-37 induces pro-angiogenic responses through TGF-β, which may act as the bridging molecule that mediates IL-37 binding to the TGF-β receptor complex.

Keywords： IL-37, TGF-β, ALK-1, Angiogenesis