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

Research output: Contribution to journalArticlepeer-review

67 Scopus citations

Abstract

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 CD11bCD103+ 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.

Original languageEnglish
Article number101760
JournalRedox Biology
Volume37
DOIs
StatePublished - Oct 2020

Bibliographical note

Funding Information:
This study was supported by GenoFocus, Inc. and the National Research Foundation (NRF) funded by the Korean government ( NRF-2012M3A9C4048761 , NRF-2020R1A3B2079811 ).

Publisher Copyright:
© 2020 The Authors

Keywords

  • Acute colitis
  • BA SOD
  • Immune response
  • p38-MAPK/NF-κB
  • ROS
  • SOD1

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