Expression data from GFP- or GFP Satellite alpha-transfected human retinal pigment epithelia cell line ARPE19

Oxidative stress (OS) and inflammation play pivotal roles in retinal pigment epithelium (RPE) degeneration and age-related macular degeneration (AMD) pathogenesis. Interleukin 17 (IL17) signaling is a founding pathway regulating inflammatory response, the IL17 ligand has been shown to induce RPE degeneration and is emerging as a potential target for AMD treatment. However, the regulation and function of IL17 receptors are largely unexplored in RPE cells under OS. Here, we identified that IL17RA was significantly upregulated in the presence of OS both in human and mouse RPE cells. We found that OS upregulates expression of reprogramming factor Kruppel-like factor 4 (KLF4), which directly binds to the IL17RA promoter and activates IL17RA transcription, therefore inducing RPE proinflammatory response. Furthermore, our results reveal that KLF4 isoform 2, but not the canonical KLF4 isoform1, is the major isoform in RPE cells that activates IL17RA transcription. Finally, we demonstrate that mRNA level of IL17RA was positively correlated with that of KLF4 isoform2 in AMD patients. Together, our data demonstrates a new regulatory mechanism of IL17RA by KLF4 upon OS exposure, which is likely to play a role in AMD pathogenesis. ARPE19 cells were transfected with GFP plasmid. Then cells were treated without (H2O2 0H) or with (H2O2 3H) 10 mU/ml glucose oxidase for 3h. Each treatment was performed in triplicates. Untreated ARPE (H2O2 0H) was considered as control group.