Herein, we show that 4-[(4-(dimethylamino)butoxy)imino]-1-methyl-1H-benzo[f]indol-9(4H)-one (CYR5099) acts as a NOX2 inhibitor and exerts a protective effect against complete Freund's adjuvant (CFA)-induced inflammatory arthritis in mice.
In this study, we generated targeted Ncf1 knock-in mice with inducible Ncf1 expression and determined the critical time window during which the NOX2-derived ROS protect the mice from arthritis.
Our results suggest that ROS act as a negative feedback to constrain IL-1β-mediated inflammation, accounting for the more severe arthritis in the absence of NOX2.
We demonstrated significantly increased NOX-2 expression in the joints of patients with inflammatory arthritis and the joints of mice with CIA as compared to controls.
The Ncf1 gene, encoding the P47(PHOX) protein that regulates production of reactive oxygen species (ROS) by the phagocyte NADPH oxidase (NOX2) complex, is associated with autoimmunity and arthritis severity in rats.