Downregulating p22phox ameliorates inflammatory response in Angiotensin II-induced oxidative stress by regulating MAPK and NF-κB pathways in ARPE-19 cells

作者：Qiu, Yiguo; Tao, Lifei; Lei, Chunyan; Wang, Jiaming; Yang, Peizeng; Li, Qiuhong; Lei, Bo^*

来源：Scientific Reports, 2015, 5(1): 14362.

DOI：10.1038/srep14362

• RETINAL-PIGMENT EPITHELIUM
• SMOOTH-MUSCLE-CELLS
• NADPH OXIDASE
• NAD(P)H OXIDASE
• ISCHEMIC RETINOPATHY
• DIABETIC-RETINOPATHY
• GENE-EXPRESSION
• UP-REGULATION
• RAT MODEL
• ACTIVATION

Oxidative stress and inflammation are two interrelated biological events implicated in the pathogenesis of many diseases. Reactive oxygen species (ROS) produced under oxidative stress play a key role in pathological conditions. Inhibition of p22phox, an indispensable component of the NADPH oxidase (NOX) complex comprising the main source of ROS, plays a protective role in many ocular conditions by inhibiting the activation of NOXs and the generation of ROS. However, little is understood regarding the role of p22phox in oxidative stress-related inflammation in the eye. We used a p22phox small interfering RNA (siRNA) to transfect the retinal pigment epithelium (RPE)-derived cell line ARPE-19, and human primary RPE (hRPE) cells, then stimulated with Ang II. We observed a potent anti-inflammatory effect and studied the underlying mechanism. Downregulating p22phox resulted in decreased ROS generation, a reduction of NOXs (NOX1, 2, 4) and a decrease in inflammatory cytokine. In addition, p22phox downregulation reduced the activation of the MAPK and NF-kappa B signaling pathways. We conclude that inhibition of p22phox has an anti-inflammatory effect in Ang II-induced oxidative stress. Suppressing the MAPK and NF-kappa B pathways is involved in this protective effect. These results suggest that p22phox may provide a promising therapeutic target for oxidative stress-induced ocular inflammation

• 出版日期2015-9-29
• 单位重庆医科大学