Oxidative stress-induced KLF4 activates inflammatory response through IL17RA and its downstream targets in retinal pigment epithelial cells.

Oxidative stress-induced KLF4 activates inflammatory response through IL17RA and its downstream targets in retinal pigment epithelial cells.
Free Radic Biol Med. 2019 Dec 24;:
Authors: Sun Q, Gong L, Qi R, Qing W, Zou M, Ke Q, Zhang L, Tang X, Nie Q, Yang Y, Hu A, Ding X, Lu L, Liu Y, Li DW
Abstract
Age-related macular degeneration (AMD) is a leading cause of irreversible blindness worldwide. Oxidative stress (OS), inflammation and genetics are considered the key pathogenic factors contribute to AMD development. Recent evidence shows the pro-inflammatory interleukin 17 (IL17) signaling is activated in AMD patients and promotes disease pathogenesis. However, the interplay between OS and IL17 signaling, and the regulatory mechanism of IL17 pathway are largely unknown. OS-induced retinal pigment epithelial cell (RPE) damage causes both the initial pathogenesis of AMD and secondary degeneration of rods and cones. Healthy RPE is essential for ocular immune privilege, however, damaged RPE cells can activate inflammatory response. In the present study, we identified IL17RA, the principle receptor of IL17 signaling, is one of the most upregulated inflammatory genes in human RPE cells upon OS exposure. The prominent increase of IL17RA was also observed in RPE and retina of an AMD-like mouse model. Knockdown of IL17RA in RPE cells prevented OS-induced RPE cell apoptosis and reduced the inflammatory response in both RPE and macrophages. Further...

Source: Free Radical Biology and Medicine - December 23, 2019 Category: Biology Authors: Sun Q, Gong L, Qi R, Qing W, Zou M, Ke Q, Zhang L, Tang X, Nie Q, Yang Y, Hu A, Ding X, Lu L, Liu Y, Li DW Tags: Free Radic Biol Med Source Type: research