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

Hwang, Jae Ho; Jin, Jing; Jeon, Sejin; Moon, Shin Hye; Park, Min Young; Yum, Do-Young; Kim, Jeong Hyun; Kang, Jieun; Park, Mi Hee; Kim, Eui-Joong; Pan, Jae-Gu; Kwon, Oran; Oh, Goo Taeg

doi:10.1016/j.redox.2020.101760

Cited by 95 publications

(76 citation statements)

References 50 publications

(32 reference statements)

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“…Under proinflammatory stimulus, the IKK complex can be activated by ROS produced by the GTP-binding protein Rac1 ( 116 ), leading to signal transduction pathways that contribute to TNF-α secretion. In line with this finding, ROS effects can be suppressed by SOD, reducing the pro-inflammatory immune responses by blocking the p38-MAPK/NF-κB signaling activation ( 117 ).…”

Section: Targets Of Ros In Macrophagesmentioning

confidence: 69%

Reactive Oxygen Species in Macrophages: Sources and Targets

et al. 2021

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Reactive oxygen species (ROS) are fundamental for macrophages to eliminate invasive microorganisms. However, as observed in nonphagocytic cells, ROS play essential roles in processes that are different from pathogen killing, as signal transduction, differentiation, and gene expression. The different outcomes of these events are likely to depend on the specific subcellular site of ROS formation, as well as the duration and extent of ROS production. While excessive accumulation of ROS has long been appreciated for its detrimental effects, there is now a deeper understanding of their roles as signaling molecules. This could explain the failure of the “all or none” pharmacologic approach with global antioxidants to treat several diseases. NADPH oxidase is the first source of ROS that has been identified in macrophages. However, growing evidence highlights mitochondria as a crucial site of ROS formation in these cells, mainly due to electron leakage of the respiratory chain or to enzymes, such as monoamine oxidases. Their role in redox signaling, together with their exact site of formation is only partially elucidated. Hence, it is essential to identify the specific intracellular sources of ROS and how they influence cellular processes in both physiological and pathological conditions to develop therapies targeting oxidative signaling networks. In this review, we will focus on the different sites of ROS formation in macrophages and how they impact on metabolic processes and inflammatory signaling, highlighting the role of mitochondrial as compared to non-mitochondrial ROS sources.

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Section: Targets Of Ros In Macrophagesmentioning

confidence: 69%

Reactive Oxygen Species in Macrophages: Sources and Targets

et al. 2021

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“…Here we suggest that an increase in SOD3 activity can improve the intestinal epithelial damage both in vitro and in vivo. Interestingly, a recent work has shown that SOD1 knockout mice exhibited increased susceptibility for DSS-induced colitis with upregulation of ROS and p38-MAPK signaling, in which oral administration of SOD could ameliorate the disease phenotype [ 39 ]. Considering the specific role and expression pattern of SOD isoforms in the intestine, it would be interesting to evaluate the therapeutic potential of SOD2- or SOD3 treatment in this model.…”

Section: Discussionmentioning

confidence: 99%

Superoxide Dismutase 3-Transduced Mesenchymal Stem Cells Preserve Epithelial Tight Junction Barrier in Murine Colitis and Attenuate Inflammatory Damage in Epithelial Organoids

Tak

Kim

Ham

et al. 2021

IJMS

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Superoxide dismutase 3 (SOD3), also known as extracellular superoxide dismutase, is an enzyme that scavenges reactive oxygen species (ROS). It has been reported that SOD3 exerts anti-inflammatory abilities in several immune disorders. However, the effect of SOD3 and the underlying mechanism in inflammatory bowel disease (IBD) have not been uncovered. Therefore, in the present study, we investigated whether SOD3 can protect intestinal cells or organoids from inflammation-mediated epithelial damage. Cells or mice were treated with SOD3 protein or SOD3-transduced mesenchymal stem cells (MSCs). Caco-2 cells or intestinal organoids stimulated with pro-inflammatory cytokines were used to evaluate the protective effect of SOD3 on epithelial junctional integrity. Dextran sulfate sodium (DSS)-induced colitis mice received SOD3 or SOD3-transduced MSCs (SOD3-MSCs), and were assessed for severity of disease and junctional protein expression. The activation of the mitogen-activated protein kinase (MAPK) pathway and elevated expression of cytokine-encoding genes decreased in TNF-α-treated Caco-2 cells or DSS-induced colitis mice when treated with SOD3 or SOD3-MSCs. Moreover, the SOD3 supply preserved the expression of tight junction (ZO-1, occludin) or adherence junction (E-cadherin) proteins when inflammation was induced. SOD3 also exerted a protective effect against cytokine- or ROS-mediated damage to intestinal organoids. These results indicate that SOD3 can effectively alleviate enteritis symptoms by maintaining the integrity of epithelial junctions and regulating inflammatory- and oxidative stress.

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“…SOD1 binds copper and zinc ions and is one of three superoxide dismutases. SOD1 deficiency in the dextran-sodium sulphate (DSS)-induced mouse model of colitis resulted in severe oxidative stress with body weight loss, epithelial barrier disruption, and decreased antioxidant enzyme activities (9). In CD, lipid peroxidation was found to correlate positively with SOD1 (10).…”

Section: Discussionmentioning

confidence: 99%

Gene Expression of Antioxidant Enzymes in the Resected Intestine in Crohn’s Disease

Sotona

Peterová

Örhalmi

et al. 2021

Acta Med. (Hradec Kralove, Czech Repub.)

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Introduction: The inflammatory process in Crohn’s disease (CD) is closely associated with the formation of reactive oxygen species. Antioxidant enzymes can play an important role in the outcome of CD and may influence postoperative recurrence in these patients. The aim of our study was to evaluate gene expression of intracellular antioxidant enzymes in surgically resected intestinal specimens of patients with CD, both in macroscopically normal and in inflamed tissue. Methods: A total of 28 patients referred for elective bowel resection were enrolled in the study. Full-thickness small intestinal specimens were investigated. Gene expression of antioxidant enzymes – superoxide dismutase (SOD), glutathione peroxidase (GPX), glutathione reductase (GSR) – was evaluated both in macroscopically normal and inflamed samples. Results: There were significantly lower levels of SOD1 mRNA (p = 0.007) and GSR mRNA (p = 0.027) in inflamed tissue compared to macroscopically normal areas. No significant differences were found between affected and non-affected intestinal segments in mRNA for SOD2, SOD3 and GPX. Conclusions: Our pilot data clearly showed that the gene expression of major antioxidant enzymes is not a uniform mechanism in the pathogenesis of Crohn’s disease. Topically decreased gene expression of SOD1 and GSR might facilitate the segmental tissue injury caused by reactive oxygen species.

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

Cited by 95 publications

References 50 publications

Reactive Oxygen Species in Macrophages: Sources and Targets

Reactive Oxygen Species in Macrophages: Sources and Targets

Superoxide Dismutase 3-Transduced Mesenchymal Stem Cells Preserve Epithelial Tight Junction Barrier in Murine Colitis and Attenuate Inflammatory Damage in Epithelial Organoids

Gene Expression of Antioxidant Enzymes in the Resected Intestine in Crohn’s Disease

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