Oxidative stress mediated by the NOX2/ROS/NF-κB signaling axis is involved in rosacea

Abstract

Rosacea is a chronic inflammatory cutaneous disease characterized by a multifaceted pathogenesis. Extensive research has demonstrated that oxidative stress plays a pivotal role in the etiology of rosacea, mediating vascular alterations and inflammation cascades via the generation of reactive oxygen species (ROS). Nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) possesses the capacity to synthesize ROS and exhibits a strong correlation with diverse inflammatory processes. However, the effects of NOX2 in rosacea are unknown. Our findings revealed that NOX2 was highly expressed in rosacea. Inhibition of NOX2 improved markedly rosacea-like manifestations, encompassing reduced skin erythema and downregulated expression of pro-inflammatory cytokines and chemokines. Additionally, knockdown NOX2 in HaCaT keratinocytes significantly rescues TNF-α-induced oxidative stress and inflammation. Our study further elucidated that inhibition of NOX2 suppressed NF-κB activation in LL37-induced skin and LL37/ TNF-α-induced HaCaT keratinocytes. Our results demonstrate that NOX2 plays a proinflammatory role in rosacea by regulating the NF-κB signaling pathway.