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

Citations Over TimeTop 14% of 2015 papers

Abstract

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-κB signaling pathways. We conclude that inhibition of p22phox has an anti-inflammatory effect in Ang II-induced oxidative stress. Suppressing the MAPK and NF-κB pathways is involved in this protective effect. These results suggest that p22phox may provide a promising therapeutic target for oxidative stress-induced ocular inflammation.

Related Papers

• → NADPH oxidase‐derived superoxide Anion‐induced apoptosis is mediated via the JNK‐dependent activation of NF‐κB in cardiomyocytes exposed to high glucose(2011)106 cited
• → Downregulating p22phox ameliorates inflammatory response in Angiotensin II-induced oxidative stress by regulating MAPK and NF-κB pathways in ARPE-19 cells(2015)44 cited
• → Role of NADPH oxidase in the apoptotic death of cultured cerebellar granule neurons(2008)53 cited
• → Endogenous production of reactive oxygen species by the NADPH oxidase complexes is a determinant of γ-glutamyltransferase expression(2011)32 cited
• → Serum of limb remote ischemic postconditioning inhibits fMLP-triggered activation and reactive oxygen species releasing of rat neutrophils(2021)4 cited