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Horm Metab Res 2018; 50(09): 704-710
DOI: 10.1055/a-0664-0699
Endocrine Research
© Georg Thieme Verlag KG Stuttgart · New York

Prostaglandin E2 Activates NLRP3 Inflammasome in Endothelial Cells to Promote Diabetic Retinopathy

Yixin Wang
1   Department of Ophthalmology, Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi, P. R. China
,
Jianxin Tao
1   Department of Ophthalmology, Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi, P. R. China
,
Yong Yao
1   Department of Ophthalmology, Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi, P. R. China
› Author Affiliations
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Publication History

received 06 March 2018

accepted 19 July 2018

Publication Date:
24 August 2018 (online)

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Abstract

Proliferative diabetic retinopathy (PDR) is the leading cause of blindness and accounts for approximately 12% of all new cases of blindness. Prostaglandin E2 (PGE2) and nucleotide-binding domain and Leucine-rich repeat Receptor containing a Pyrin domain 3 (NLRP3) inflammasomes have been long considered to be associated with PDR. Levels of pro-inflammatory mediators were examined by Enzyme-linked immunosorbent assay (ELISA) measurements. PGE2 levels were analyzed by using the Prostaglandin E2 Monoclonal EIA Kit. Human retinal microvascular endothelial cells (HRMECs) were stained with Annexin V/propidium iodide and analyzed by flow cytometry for testing the apoptosis. Expression levels of NLRP3 inflammasome components under various conditions were detected by Western blot and real-time PCR. Inflammasome markers and PGE2 were highly expressed in the vitreous of PDR patients. PGE2 and NLRP3 induced apoptosis of HRMECs. PGE2 upregulated the expression of NLRP3 inflammasome components and inflammatory chemokines. Knockdown of NLRP3 attenuated the expression of NLRP3 inflammasome components and inhibited the effect of PGE2. Our results suggest that PGE2 levels and NLRP3 inflammasome activation are closely related to the pathogenesis of PDR and nonsteroidal anti-inflammatory drugs may have a potential therapeutic effect on PDR.

Key words

proliferative diabetic retinopathy (PDR) - NLRP3 inflammasomes - prostaglandin E2 (PGE2) - apoptosis
 

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