期刊
INTERNATIONAL IMMUNOPHARMACOLOGY
卷 66, 期 -, 页码 162-168出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.intimp.2018.10.040
关键词
Linagliptin; Retinal endothelial cells (RECs); TNF-alpha; NF-kB; Vascular protection
资金
- Sichuan Provincial Health and Family Planning Commission [17PJ551]
People with diabetes are at high risk of developing diabetes-related eye disease, termed as diabetic retinopathy, due damage being caused to the blood vessels in the retina. An efficient medical treatment to reduce diabetic retinopathy can improve the quality of life for diabetes patients. In our study, we show that linagliptin, a commercially available DPP-4 inhibitor, plays a protective role in retinal vascular endothelial cells. The presence of linagliptin protects retinal endothelial cells against TNF-alpha-induced cytotoxicity and enhances their viability. Linagliptin treatment suppresses TNF-alpha-induced production of reactive oxygen species and improves mitochondrial membrane potential. Moreover, linagliptin suppresses TNF-alpha-induced production of pro-inflammatory and pro-adhesive vascular cytokines including IL-6, IL-8, ICAM-1, and VCAM-1. The presence of linagliptin in cell media can reduce the number of THP-1 cells that adhere to retina endothelial cells. Mechanistically, linagliptin potently suppresses TNF-alpha-induced accumulation of NF-kappa B nuclear protein p65 and activation of NF-kappa B promoter. Our data indicate that linagliptin is an anti-inflammatory diabetic agent, with the potential to be applied as a treatment for diabetic retinopathy.
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