Involvement of IL-37 in the Pathogenesis of Proliferative Diabetic Retinopathy.
Interleukin-37 is suggested as a novel proangiogenic factor in our previous study. In this study, the role of IL-37 was investigated in proliferative diabetic retinopathy (PDR).



Vitreous fluids from 10 patients with PDR and 8 controls were collected. The levels of IL-37 were determined by ELISA and the relationship between IL-37 and VEGF-A/Ang-2 was analyzed. The effects of IL-37 on chorioretinal endothelial cell (RF/6A) proliferation, migration, and tube formation were determined by BrdU incorporation assay, Boyden chamber assay, scratch-wound assay and tube formation assay.



The concentration of IL-37 in the PDR group was 95.09 ± 5.22 pg/mL and 34.91 ± 5.61 pg/mL in control group (P = 0.001). The level of IL-37 was highly related to the level of Ang-2 (P = 0.009, r = 0.772) and VEGF-A (P = 0.003, r = 0.827) in the PDR group, and VEGF expression in RF/6A cell was upregulated by IL-37 at low concentration. Interleukin-37 remarkably promoted RF/6A cell proliferation and migration. Interleukin-37 (1 ng/mL) remarkably stimulated tube formation with an increase of 85.3% for total tubule length and 74.1% for branching points compared with PBS control.



The level of IL-37 is elevated in vitreous fluids of patients with PDR and correlates with the level of VEGF-A and Ang-2. Interleukin-37 stimulates proangiogenic response of retinal endothelial cells in vitro, suggesting the involvement of IL-37 in the pathogenesis of PDR.
Shanghai Tenth People's Hospital Tongji University School of Medicine, Shanghai, China.
Mengmeng
M
Zhao
Shanghai Tenth People's Hospital Tongji University School of Medicine, Shanghai, China.
Yongguang
Y
Hu
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.
Ying
Y
Yu
Shanghai Tenth People's Hospital Tongji University School of Medicine, Shanghai, China 3Johns Hopkins University School of Medicine, Baltimore, Maryland, United States.
Qing
Q
Lin
Shanghai Tenth People's Hospital Tongji University School of Medicine, Shanghai, China.
Jianhua
J
Yang
Shanghai Tenth People's Hospital Tongji University School of Medicine, Shanghai, China.
Shao Bo
SB
Su
Department of Ophthalmology, Shanghai Tenth People Hospital, and Tongji Eye Institute, Tongji University School of Medicine, Shanghai, China.
Guo-Tong
GT
Xu
Shanghai Tenth People's Hospital Tongji University School of Medicine, Shanghai, China.
Tianshu
T
Yang
D000368:Aged; D042702:Angiopoietin-2 / Q000378:metabolism; D016022:Case-Control Studies; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D002478:Cells, Cultured; D003930:Diabetic Retinopathy / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014822:Vitreous Body / Q000378:metabolism*
D042702:Angiopoietin-2; C508587:IL37 protein, human; D007375:Interleukin-1; D042461:Vascular Endothelial Growth Factor A