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

Yixin Wang; Jianxin Tao; Yong Yao

doi:10.1055/a-0664-0699

Hormone and Metabolic Research, Table of Contents

Horm Metab Res 2018; 50(09): 704-710
DOI: 10.1055/a-0664-0699

Endocrine Research

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

Authors

Yixin Wang

¹Department of Ophthalmology, Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi, P. R. China
Jianxin Tao

¹Department of Ophthalmology, Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi, P. R. China
Yong Yao

¹Department of Ophthalmology, Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi, P. R. China

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

Full Text

References

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