SOD1 suppresses pro-inflammatory immune responses by protecting against oxidative stress in colitis
Jiyoung Hwang,
Jing Jin,
Sejin Jeon,
Shin Hye Moon,
Min Young Park,
Do-Young Yum,
Jeong Hyun Kim,
Ji-Eun Kang,
Mi Hee Park,
Eui-Joong Kim,
Jae-Gu Pan,
Oran Kwon,
Goo Taeg Oh
Affiliations
Jiyoung Hwang
Department of Nutritional Science and Food Management, Ewha Womans University, 52 Ewhayeodae-gil, Seodeamun-gu, Seoul, 03760, Republic of Korea
Jing Jin
Immune and Vascular Cell Network Research Center, National Creative Initiatives, Department of Life Sciences, Ewha Womans University, 52 Ewhayeodae-gil, Seodeamun-gu, Seoul, 03760, Republic of Korea
Sejin Jeon
Immune and Vascular Cell Network Research Center, National Creative Initiatives, Department of Life Sciences, Ewha Womans University, 52 Ewhayeodae-gil, Seodeamun-gu, Seoul, 03760, Republic of Korea
Shin Hye Moon
Immune and Vascular Cell Network Research Center, National Creative Initiatives, Department of Life Sciences, Ewha Womans University, 52 Ewhayeodae-gil, Seodeamun-gu, Seoul, 03760, Republic of Korea
Min Young Park
Department of Nutritional Science and Food Management, Ewha Womans University, 52 Ewhayeodae-gil, Seodeamun-gu, Seoul, 03760, Republic of Korea
Do-Young Yum
GenoFocus, Inc., 65, Techno 1-ro, Yuseong-gu, Daejeon, 34014, Republic of Korea
Jeong Hyun Kim
GenoFocus, Inc., 65, Techno 1-ro, Yuseong-gu, Daejeon, 34014, Republic of Korea
Ji-Eun Kang
GenoFocus, Inc., 65, Techno 1-ro, Yuseong-gu, Daejeon, 34014, Republic of Korea
Mi Hee Park
GenoFocus, Inc., 65, Techno 1-ro, Yuseong-gu, Daejeon, 34014, Republic of Korea
Eui-Joong Kim
GenoFocus, Inc., 65, Techno 1-ro, Yuseong-gu, Daejeon, 34014, Republic of Korea
Jae-Gu Pan
GenoFocus, Inc., 65, Techno 1-ro, Yuseong-gu, Daejeon, 34014, Republic of Korea
Oran Kwon
Department of Nutritional Science and Food Management, Ewha Womans University, 52 Ewhayeodae-gil, Seodeamun-gu, Seoul, 03760, Republic of Korea; Corresponding author.
Goo Taeg Oh
Immune and Vascular Cell Network Research Center, National Creative Initiatives, Department of Life Sciences, Ewha Womans University, 52 Ewhayeodae-gil, Seodeamun-gu, Seoul, 03760, Republic of Korea; Corresponding author.
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.
