SOD1 suppresses pro-inflammatory immune responses by protecting against oxidative stress in colitis

Superoxide dismutase 1 (SOD1) binds copper and zinc ions and is one of three superoxide dismutases responsible for destroying free superoxide radicals in the body. Reactive oxygen species (ROS), including free superoxide radicals, play important roles in colitis. However, the role of SOD1 in oxidative stress under colitis remains unclear. Here, we examined the role of SOD1 in the DSS-induced mouse model of colitis. SOD1 deficiency resulted in severe oxidative stress with body weight loss, epithelial barrier disruption and decreased antioxidant enzyme activities. The levels of neutrophils, monocytes, pro-inflammatory CD11c+ macrophages and CD11b+CD103- dendritic cells (DCs) were increased, while anti-inflammatory CD206+ macrophages and CD11b−CD103+ DCs were decreased, in DSS-treated SOD1-knockout (KO) mice compared to DSS-treated wild-type mice. Furthermore, rescue of SOD activity in SOD1-KO mice by oral gavage of B. amyloliquefaciens SOD (BA SOD) significantly ameliorated enhanced DSS-induced colitis in these mice by suppressing p38-MAPK/NF-κB signaling, which can induce inflammation and apoptosis. Taken together, our results suggest that SOD1-mediated inhibitory responses play a crucial role in limiting the development of DSS-induced colitis, and that BA SOD is a promising candidate for treating colitis. [Display omitted] •Superoxide dismutase 1(SOD1) deficiency exacerbates DSS-induced colitis.•SOD1 deficiency increases ROS production and reduces antioxidant enzyme activities.•SOD1 deficiency increases the infiltration of pro-inflammatory immune cells.•Rescue of SOD1 by BA SOD administration ameliorates acute colitis.•BA SOD administration suppresses p38-MAPK/NF-κB signaling.