NADPH Oxidases in Inflammatory Bowel Disease

Stenke, Emily; Bourke, Billy; Knaus, Ulla G.

doi:10.1007/978-1-4939-9424-3_38

Cited by 18 publications

(11 citation statements)

References 101 publications

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“… 10 Consistent with these important physiological functions, dysregulation of NOX1 by loss-of-function or excessive activity may cause pathologic conditions in the gastrointestinal tract such as inflammatory bowel disease (IBD), a group of chronic and relapsing disorders comprising Crohn’s disease (CD) and ulcerative colitis (UC) that are characterized by severe inflammation of the intestines. NOX1 gene variants associated with loss of function have been described in human very early-onset IBD 11 ; however, overexpression of NOX1 and NOXO1 has also been observed in UC and CD. 8 , 12 …”

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confidence: 99%

Protein Kinase CK2 Acts as a Molecular Brake to Control NADPH Oxidase 1 Activation and Colon Inflammation

Liú

Marie²,

Pelletier³

et al. 2022

Cellular and Molecular Gastroenterology and Hepatology

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confidence: 99%

Protein Kinase CK2 Acts as a Molecular Brake to Control NADPH Oxidase 1 Activation and Colon Inflammation

Liú

Marie²,

Pelletier³

et al. 2022

Cellular and Molecular Gastroenterology and Hepatology

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“…Inhibition of NET release (through DNase administration) ameliorated colitis as well as colitis-associated tumorigenesis [ 58 ]. In addition, neutrophils are one of the major source of reactive oxygen species (ROS) which trigger tissue injury and lead to chronic inflammation and tumorigenesis [ 59 , 60 ]. Reducing the degree of ROS by various means was shown to reduce colitis severity [ 61 – 66 ].…”

Section: Discussionmentioning

confidence: 99%

Onion bulb extract can both reverse and prevent colitis in mice via inhibition of pro-inflammatory signaling molecules and neutrophil activity

et al. 2020

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Background Onion is one of the most commonly used plants in the traditional medicine for the treatment of various diseases. We recently demonstrated the anti-inflammatory properties of onion bulb extract (OBE) in reducing colitis severity in mice when administered at the same time of colitis induction. However, whether onion can reverse established colitis or even prevent its development has not been investigated. Hypothesis To test 1. whether OBE can reduce colitis severity when given either before (preventative approach) or after (treatment approach) colitis induction and if so, 2. what are the mechanisms by which onion can achieve these effects. Methods Colitis was induced by dextran sulfate sodium (DSS) administration using treatment and preventative approaches. The severity of the inflammation was determined by the gross and histological assessments. The colonic level/activity of pro-inflammatory molecules and immune cell markers was assessed by immunofluorescence and western blotting analysis. In vitro neutrophil superoxide release and survival was assessed by chemilumenecense and Annexin-V/7AAD assays respectively. Results OBE treatment significantly reduced colitis severity in both approaches, the colonic expression/activity profile of pro-inflammatory molecules, inhibited WKYMVm-induced superoxide release, and increased spontaneous apoptosis of neutrophils in vitro . Conclusions OBE can be used as an effective option in the prevention and/or the treatment of established colitis.

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“…However, loss-of-function variants in NOX2 complex components that decrease or abrogate superoxide generation induce hyperinflammation in chronic granulomatous disease (CGD) patients with 40–50% of patients developing CGD-IBD over time [ 39 , 40 ]. Similarly, decreased superoxide or H 2 O 2 generation by NOX1 and DUOX2 variants has been associated with chronic inflammation in very early onset IBD patients [ 41 ]. These and many other observations point to a homeostatic range of ROS as essential for maintaining intestinal health, while persistently increased or decreased ROS levels perpetuate inflammation.…”

Section: Discussionmentioning

confidence: 99%

NADPH oxidase 4 is protective and not fibrogenic in intestinal inflammation

et al. 2020

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Dysregulated redox signaling and oxidative injury are associated with inflammatory processes and fibrosis. H 2 O 2 generation by NOX4 has been suggested as a key driver in the development of fibrosis and a small molecule drug is under evaluation in clinical trials for idiopathic pulmonary fibrosis and primary biliary cholangitis. Fibrosis is a common complication in Crohn's disease (CD) leading to stricture formation in 35–40% of patients, who require surgical interventions in the absence of therapeutic options. Here we assess NOX4 expression in CD patients with inflammatory or stricturing disease and examine whether loss of NOX4 is beneficial in acute and fibrotic intestinal disease. NOX4 was upregulated in inflamed mucosal tissue of CD and ulcerative colitis (UC) patients, in CD ileal strictures, and in mice with intestinal inflammation. Nox4 deficiency in mice promoted pathogen colonization and exacerbated tissue injury in acute bacterial and chemical colitis. In contrast, in two chronic injury models aberrant tissue remodeling and fibrosis-related gene expression did not differ substantially between Nox4 −/− mice and wildtype mice, suggesting that Nox4 is dispensable in TGF-β1-driven intestinal fibrogenesis. While animal models do not recapitulate all the hallmarks of CD fibrosis, the tissue-protective role of Nox4 warrants a cautious approach to pharmacological inhibitors.

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NADPH Oxidases in Inflammatory Bowel Disease

Cited by 18 publications

References 101 publications

Protein Kinase CK2 Acts as a Molecular Brake to Control NADPH Oxidase 1 Activation and Colon Inflammation

Protein Kinase CK2 Acts as a Molecular Brake to Control NADPH Oxidase 1 Activation and Colon Inflammation

Onion bulb extract can both reverse and prevent colitis in mice via inhibition of pro-inflammatory signaling molecules and neutrophil activity

NADPH oxidase 4 is protective and not fibrogenic in intestinal inflammation

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