Deficiency in Duox2 activity alleviates ileitis in GPx1- and GPx2-knockout mice without affecting apoptosis incidence in the crypt epithelium

Chu, Fong‐Fong; Esworthy, R. Steven; Doroshow, James H.; Grasberger, Helmut; Donkó, Ágnes; Leto, Thomas L.; Gao, Qiang; Shen, Binghui

doi:10.1016/j.redox.2016.11.001

Cited by 35 publications

(46 citation statements)

References 66 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…DUOX2 induces exfoliation of the crypt epithelium, which is a major contributor to inflammation. Therefore, DUOX2 may be a potential therapeutic target for treating ileocolitis inflammatory bowel disease (Chu et al, 2017). Helicobacter pylori infection causes the most common human chronic infection.…”

Section: Duox Immune Function In the Digestive Tractmentioning

confidence: 99%

Mini review: immunologic functions of dual oxidases in mucosal systems of vertebrates

2020

View full text Add to dashboard Cite

Mucosal epithelial cells act as the first immunologic barrier of organisms, and contact directly with pathogens. Therefore, hosts must have differential strategies to combat pathogens efficiently. Reactive oxygen species (ROS), as a kind of oxidizing agents, participates in the early stage of killing pathogens quickly. Recent reports have revealed that dual oxidase (DUOX) plays a key role in mucosal immunity. And the DUOX is a transmembrane protein which produces ROS as their primary enzymatic products. This process is an important pattern for eliminating pathogens. In this review, we highlight the DUOX immunologic functions in the respiratory and digestive tract of vertebrates.

show abstract

Section: Duox Immune Function In the Digestive Tractmentioning

confidence: 99%

Mini review: immunologic functions of dual oxidases in mucosal systems of vertebrates

2020

View full text Add to dashboard Cite

show abstract

“…Evidently, Cyp4a14 does not affect Nox gene expression, since the mRNA levels of all four members, Nox1, Nox2, Nox4 and Duox2, were the same in the colon of both KO and WT mice, with and without DSS treatment. However, DSS markedly decreased the mRNA levels of Nox1 and Doux2, two epithelium-specific enzymes that are involved in the pathogenesis of IBD [26,50]. The downregulation of Nox1 and Duox2 gene expression is most likely due to the loss of epithelial cells.…”

Section: Discussionmentioning

confidence: 92%

“…20-Hydroxyeicosatetraenoic acid (20-HETE) is one of the primary eicosanoids metabolized by the CYP4A subfamily and can induce the expression of the gp91 and p22phox subunits of Nox2, a member of NADPH oxidase (NOX, Nox in animal) in cardiomyocytes [23,24]. Since oxidative stress clearly plays a key role in the pathogenesis of IBD, as shown by spontaneous ileocolitis developing in mice deficient in antioxidant enzymes [25,26], we also evaluated the effect of Cyp4a14 on several members Cellular Physiology and Biochemistry…”

Section: Introductionmentioning

confidence: 99%

Mice Deficient in Cyp4a14 Have An Increased Number of Goblet Cells and Attenuated Dextran Sulfate Sodium-Induced Colitis

Xuan¹,

Zhou²,

Tan³

et al. 2018

Cell Physiol Biochem

Self Cite

View full text Add to dashboard Cite

Background/Aims: Cyp4a14 is a member of cytochrome P450 (Cyp450) enzyme superfamily that possesses NADPH monooxygenase activity, which catalyzes omega-hydroxylation of medium-chain fatty acids and arachidonic acid. Study suggests that down-regulation of Cyp4a14 has an anti-inflammatory response in intestine. The present study was to test the function of Cyp4a14 in dextran sulfate sodium (DSS)-induced colitis. Methods: Female Cyp4a14-knockout (KO) and wild-type (WT) mice were treated with DSS for 6 days to induce colitis. The colon of mice was histologically observed by hematoxylin and eosin (H&E) and periodic acid Schiff (PAS) staining. The serum malondialdehyde (MDA), an endogenous indicator of oxidative stress, was chemically measured. Proinflammatory and NADPH oxidase genes were examined by quantitative polymerase chain reaction (qPCR). Results: Cyp4a14-KO mice had a significantly higher number of goblet cells in the colon and were more resistant to DSS-induced colitis compared with the WT mice. The DSS-treated KO mice had lower levels of MDA. Consistent with the milder inflammatory pathological changes, DSS-treated KO mice had lower levels of IL-1β, IL-6 and TNF-α mRNA in the liver and the colon. Moreover, the colon of DSS-treated Cyp4a14-KO and WT mice had higher mRNA levels of two members of NADPH oxidases, Nox2 and Nox4, suggesting that both Nox2 and Nox4 are inflammatory markers. By contrast, DSS-treated WT and KO mice had drastically decreased epithelium-localized Nox1 and dual oxidase (Duox) 2 mRNA levels, coinciding with the erosion of the mucosa induced by DSS. Conclusion: These results suggests a hypothesis that the increased goblet cell in the colon of Cyp4a14-KO mice provides protection from mucosal injury and Cyp4a14-increased oxidative stress exacerbates DSS-induced colitis. Therefore, Cyp4a14 may represent a potential target for treating colitis.

show abstract

“…Some of these genes, such as DUOX2 and DUOXA2, have been found to play a role in bacterial sensing and exhibit increased expression in the ilea of CD patients (45). In fact, DUOX2 drives ileitis in transgenic mice lacking glutathione peroxidase 1 and 2 (54). Many aspects of intestinal physiology and immune homeostasis are sensitive to the microbiota.…”

Section: Discussionmentioning

confidence: 99%

Microbiota-sensitive epigenetic signature predicts inflammation in Crohn’s disease

Kelly¹,

Kotliar²,

Woo³

et al. 2018

JCI Insight

View full text Add to dashboard Cite

Altered response to the intestinal microbiota strongly associates with inflammatory bowel disease (IBD); however, how commensal microbial cues are integrated by the host during the pathogenesis of IBD is not understood. Epigenetics represents a potential mechanism that could enable intestinal microbes to modulate transcriptional output during the development of IBD. Here, we reveal a histone methylation signature of intestinal epithelial cells isolated from the terminal ilea of newly diagnosed pediatric IBD patients. Genes characterized by significant alterations in histone H3-lysine 4 trimethylation (H3K4me3) showed differential enrichment in pathways involving immunoregulation, cell survival and signaling, and metabolism. Interestingly, a large subset of these genes was epigenetically regulated by microbiota in mice and several microbiota-sensitive epigenetic targets demonstrated altered expression in IBD patients. Remarkably though, a substantial proportion of these genes exhibited H3K4me3 levels that correlated with the severity of intestinal inflammation in IBD, despite lacking significant differential expression. Collectively, these data uncover a previously unrecognized epigenetic profile of IBD that can be primed by commensal microbes and indicate sensitive targets in the epithelium that may underlie how microbiota predispose to subsequent intestinal inflammation and disease.

show abstract

Deficiency in Duox2 activity alleviates ileitis in GPx1- and GPx2-knockout mice without affecting apoptosis incidence in the crypt epithelium

Cited by 35 publications

References 66 publications

Mini review: immunologic functions of dual oxidases in mucosal systems of vertebrates

Mini review: immunologic functions of dual oxidases in mucosal systems of vertebrates

Mice Deficient in Cyp4a14 Have An Increased Number of Goblet Cells and Attenuated Dextran Sulfate Sodium-Induced Colitis

Microbiota-sensitive epigenetic signature predicts inflammation in Crohn’s disease

Contact Info

Product

Resources

About