Inhibition of NADPH oxidase activities ameliorates DSS-induced colitis

NADPH oxidases (NOX) act to generate reactive oxygen species (ROS) and exhibit microbicidal bioactivity, whereas their roles in mediating immune responses of inflammation in intestine remain to be further elucidated. The study was performed to explore the effects of NOX activity on regulation of macrophage functions. Macrophage responses were induced by lipopolysaccharides (LPS) in RAW 264.7 cells (in vitro) or dextran sulfate sodium (DSS) in BALB/c mice (in vivo) respectively. LPS induced NOX2 expression and initiated NOX activities in RAW 264.7 cells. Conversely, inhibition of NOX activity by DPI and VAS2870 diminished LPS induced NOX activities and the downstream signaling in RAW 264.7 cells. Murine colitis was characterized by macrophage accumulation and elevation of NOX activities in colon tissues. DPI and VAS2870 administration overrode NOX activities and ROS productions in colon tissues, and ameliorated DSS-induced colitis evidenced with the reduced disease activities and the decreased cytokine levels. Intriguingly, NOX2 expression levels were elevated in colon tissues of patients with active inflammatory bowel disease. Together, our data show a crucial role of NOX activity in regulation of macrophage functions and responses, and suggest that NOX represents a novel therapeutic approach for the management of immune diseases.