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Arterioscler Thromb Vasc Biol. 2015 Dec;35(12):2638-46. doi: 10.1161/ATVBAHA.115.306543. Epub 2015 Oct 29.

IL-37 Is a Novel Proangiogenic Factor of Developmental and Pathological Angiogenesis.

Author information

1
From the Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China (T.Y., Q.L., M.Z., Y.H., R.W., X.Z., G.X., J.Y., S.B.S.); Johns Hopkins University School of Medicine, Baltimore, MD (Q.L., X.Y.); State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China (Y.Y., J.J., H.Z., X.H., S.B.S., X.L.); Department of Ophthalmology, the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China (G.L., P.L.); Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX (D.B.C.); and Department of Stomatology, Huashan Hospital, Fudan University, Shanghai, China (S.L.). tianshuy@tongji.edu.cn shangfengliufudan@163.com liuxl28@mail.sysu.edu.cn.
2
From the Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China (T.Y., Q.L., M.Z., Y.H., R.W., X.Z., G.X., J.Y., S.B.S.); Johns Hopkins University School of Medicine, Baltimore, MD (Q.L., X.Y.); State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China (Y.Y., J.J., H.Z., X.H., S.B.S., X.L.); Department of Ophthalmology, the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China (G.L., P.L.); Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX (D.B.C.); and Department of Stomatology, Huashan Hospital, Fudan University, Shanghai, China (S.L.).

Abstract

OBJECTIVE:

Angiogenesis is tightly controlled by growth factors and cytokines in pathophysiological settings. Interleukin 37 (IL-37) is a newly identified cytokine of the IL-1 family, some members of which are important in inflammation and angiogenesis. However, the function of IL-37 in angiogenesis remains unknown. We aimed to explore the regulatory role of IL-37 in pathological and physiological angiogenesis.

APPROACH AND RESULTS:

We found that IL-37 was expressed and secreted in endothelial cells and upregulated under hypoxic conditions. IL-37 enhanced endothelial cell proliferation, capillary formation, migration, and vessel sprouting from aortic rings with potency comparable with that of vascular endothelial growth factor. IL-37 activates survival signals including extracellular signal-regulated kinase 1/2 and AKT in endothelial cells. IL-37 promoted vessel growth in implanted Matrigel plug in vivo in a dose-dependent manner with potency comparable with that of basic fibroblast growth factor. In the mouse model of retinal vascular development, neonatal mice administrated with IL-37 displayed increased neovascularization. We demonstrated further that IL-37 promoted pathological angiogenesis in the mouse model of oxygen-induced retinopathy.

CONCLUSIONS:

Our findings suggest that IL-37 is a novel and potent proangiogenic cytokine with essential role in pathophy siological settings.

KEYWORDS:

cytokines; endothelial cell; inflammation; interleukins; oxygen-induced retinopathy

PMID:
26515414
DOI:
10.1161/ATVBAHA.115.306543
[Indexed for MEDLINE]

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