Interleukin-17A Induces IL-1β Secretion From RPE Cells Via the NLRP3 Inflammasome

Investigative Ophthalmology & Visual Science
Shujie ZhangJihong Wu

Abstract

Inflammasome activation and IL-1β production have been proposed to have an important role in age-related macular degeneration (AMD). Growing evidence is emerging for involvement of interleukin-17A (IL-17A) in AMD pathogenesis. We investigated the effects of IL-17A on the activation of inflammasome and production of IL-1β in primary human RPE cells. Primary human RPE cells were isolated and cultured for the following experiments. Expression patterns of IL-17 receptor A (IL-17RA), IL-17 receptor C (IL-17RC), and ACT1 were analyzed by RT-PCR, flow cytometry, and immunofluorescence. IL-17A was added to the cell cultures, and cytokine expression, signaling pathways, and inflammasome machinery were investigated using real-time RT-PCR, ELISA, Western blot, flow cytometry, and small interfering RNA. Retinal pigment epithelial cells constitutively expressed IL-17RA, IL-17RC, and ACT1. IL-17A upregulated the mRNA levels of pro-IL-1β, IL-8, CCL2, and CCL20, as well as the protein level of IL-1β. IL-17A induced the phosphorylation of Akt, Erk1/2, p38 MAPK, and NF-κB p65 in RPE cells. Blocking NF-κB attenuated IL-17A-induced expression of pro-IL-1β mRNA. IL-17A enhanced pro-caspase-1 and NLRP3 mRNA expression. Inhibiting caspase-1 activity ...Continue Reading

Citations

Jul 5, 2016·International Journal of Environmental Research and Public Health·Mei-Hua BaoJian-Ming Li
Nov 21, 2017·Pathobiology of Aging & Age Related Diseases·Jacob HarrisTorben L Sørensen
Jul 20, 2018·Investigative Ophthalmology & Visual Science·David A CoplandAndrew D Dick
Jan 16, 2019·Investigative Ophthalmology & Visual Science·Marie Krogh NielsenTorben Lykke Sørensen
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Jul 22, 2017·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Zhenyang ZhaoJiyang Cai
Feb 6, 2020·International Journal of Molecular Sciences·Rayne R LimShyam S Chaurasia
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Nov 7, 2019·Clinical Kidney Journal·Dongsheng ChengFeng Wang
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Jul 11, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Kang-Yun LuHorng-Jyh Harn

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