The Role of Myeloperoxidase and Neutrophil Extracellular Traps in the Pathogenesis of Inflammatory Bowel Disease

Chami, Belal; Ahmad, Gulfam; Schroder, Angie L; Gabriel, Patrick San; Witting, Paul K.

doi:10.1053/j.gastro.2021.01.044

Cited by 10 publications

(7 citation statements)

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“…Inflammation-led neutrophil production of MPO converts H 2 O 2 into hypochlorous acid (HOCl) ROS, which aggravates the mucosal injury. 63 Our assessment indicated elevated iNOS, NO, LPO-MDA, and MPO oxidative species levels and decreased concentrations of the antioxidants GSH, GST, and catalase in the DSS-colitis mice. Tofa-P/tfr NC treatment successfully diminished ROS and increased antioxidants (Fig.…”

Section: Discussionmentioning

confidence: 63%

QbD-based fabrication of transferrin-anchored nanocarriers for targeted drug delivery to macrophages and colon cells for mucosal inflammation healing

et al. 2023

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Section: Discussionmentioning

confidence: 63%

QbD-based fabrication of transferrin-anchored nanocarriers for targeted drug delivery to macrophages and colon cells for mucosal inflammation healing

et al. 2023

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“…In addition, the use of Cl-amidine and striptonigrin, a generic PAD inhibitor and a selective PAD4 inhibitor respectively, has demonstrated to reduce the inflammatory burden in a mouse DSS model of acute colitis 58,61 . Other authors have also claimed a similar effect by using an inhibitor of myeloperoxidase (MPO) 62 . Very recently, NETs localisation has also been reported in perianal fistulas of CD patients, with particular abundance in the ones with unhealed post-operative fistulas 63 .…”

Section: Nets and Ibdmentioning

confidence: 84%

“…68 (61)(62)(63)(64)(65)(66)(67)(68)(69)(70)(71)(72)(73)(74)(75)(76) unaffected, inflamed, or fibrotic tissue. The results are reported in Figure 7a and Figure 7b for the Inflammation score and the Fibrosis score, respectively.…”

Section: Age At Surgery (Median Iqr)mentioning

confidence: 99%

461: The Profibrogenic Role of Neutrophil Extracellular Traps in Stenotic Crohn's Disease: A New Antifibrotic Target?

Dragoni¹,

Ke²,

Verstockt³

et al. 2022

Gastroenterology

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“…As NO in combination with superoxide anion yields massive amounts of peroxynitrite radical that inflicts necrosis likely through lipid oxidation and DNA fragmentation (Soufli et al 2016 ; Cross and Wilson 2003 ). The MPO enzyme is a pivotal factor in the induction of oxidative stress in the colon, as it leads to the overproduction of hypochlorous acid, a highly reactive oxidant that exerts cytotoxic effects and contributes to the pathophysiological manifestations of UC (Chami et al 2021 ; Yang et al 2023 ).…”

Section: Discussionmentioning

confidence: 99%

Management of ulcerative colitis by dichloroacetate: Impact on NFATC1/NLRP3/IL1B signaling based on bioinformatics analysis combined with in vivo experimental verification

Abdel-Razek,

Mahmoud,

Azouz

2023

Inflammopharmacol

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The inflammatory response in ulcerative colitis (UC) could be relieved by the conventional immunomodulatory agents; 5-aminosalicylic acid, corticosteroids, or azathioprine. However, the low remission rates and the intolerance to these agents necessitate investigation of gene expression signature in UC that could influence the therapeutic efficacy of drugs, as well as the interference with persistence genes by novel therapeutic option. Three microarray datasets (GSE66407, GSE38713 and GSE14580) from the NCBI-GEO database were utilized. Differentially expressed genes between samples of patients with UC and healthy ones were analyzed using R software. In addition, in vivo study using oxazolone-induced UC in BALB/c mice was carried out to investigate the proposed therapeutic efficacy of dichloroacetate (DCA). The bioinformatics analysis revealed the persistence of NLRP3, NFATC1, and IL1B in UC despite treatment with common therapeutic agents. DCA administration to oxazolone-treated mice showed remarkable interference with those persistence genes. Western blotting analysis for NLRP3, NFATC1, nuclear/total NF-κB, and cleaved caspase-1 revealed the ability of DCA to reduce the expression levels of these proteins in oxazolone-treated mice. Additionally, the inflammatory cytokines IL-1β and IL-13 were reduced in colonic tissue by DCA treatment. The therapeutic efficacy of DCA was further confirmed by the apparent reduction in histopathological scoring, disease activity index, and the normalization of colon length. Therefore, DCA could be suggested as a novel and promising therapeutic option in UC based on its ability to interfere with the persistence of NFATC1/NLRP3/IL1B signaling. That merits further safety/toxicological pre-clinical assessment and update of bioavailability/metabolism data prior to clinical investigation.

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The Role of Myeloperoxidase and Neutrophil Extracellular Traps in the Pathogenesis of Inflammatory Bowel Disease

Cited by 10 publications

References 0 publications

QbD-based fabrication of transferrin-anchored nanocarriers for targeted drug delivery to macrophages and colon cells for mucosal inflammation healing

QbD-based fabrication of transferrin-anchored nanocarriers for targeted drug delivery to macrophages and colon cells for mucosal inflammation healing

461: The Profibrogenic Role of Neutrophil Extracellular Traps in Stenotic Crohn's Disease: A New Antifibrotic Target?

Management of ulcerative colitis by dichloroacetate: Impact on NFATC1/NLRP3/IL1B signaling based on bioinformatics analysis combined with in vivo experimental verification

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