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Volume 8
Journal of Gastrointestinal & Digestive System
ISSN: 2161-069X
Gastro Congress 2018
August 20-21, 2018
Page 42
conference
series
.com
August 20-21, 2018 | Rome, Italy
13
th
Euro-Global
Gastroenterology Conference
Fong Fong Chu, J Gastrointest Dig Syst 2018, Volume 8
DOI: 10.4172/2161-069X-C5-075
Reactive oxygen species generated by NADPH oxidase-1 and Dual oxidase-2 contribute to
inflammatory bowel disease
Statement of the Problem:
Gut microbes play an essential role in pathogenesis of inflammatory bowel disease (IBD). Host cells respond
to microbe colonization by releasing cytokines and chemokines. Some inflammatory cytokines such as IL-4 and IL-13 induce NADPH
oxidase-1 (NOX1) and dual oxidase-2 (DUOX2) gene expression in the epithelial cells. Elevated NOX1 or DUOX2 can produce reactive
oxygen species (ROS) to regulate various cellular functions including cell proliferation, migration and apoptosis. NOX1 and DUOX2
have been linked to very-early-onset IBD, beginning before 6 years old. But the exact role of NOX1 and DUOX2 in IBD is not known.
Methodology:
Mice deficient in antioxidant enzymes, glutathione peroxidase (GPx)-1 and -2, so called GPx1/2-DKO mice, develop
ileocolitis around weaning. The hall-mark of pathology includes high crypt apoptosis, Paneth cell depletion, exfoliation and crypt
abscess. Germ-free DKO mice are disease-free. To explore the role of Nox1 and Duox2 in gut inflammation, we studied the pathology
and phenotype of Nox1-GPx1/2-triple KO (TKO) and Duox-GPx1/2-TKO mice at 35 days of age (comparable to human very-early-
onset IBD).
Findings:
Nox1-Gpx1/2-TKO mice virtually do not have pathology. Duox-GPx1/2-TKO mice have intermediate pathology except
crypt apoptosis remain as high as the DKO mice.
Conclusions & Significance:
Both Nox1 and Duox2 contribute to inflammation, while Nox1 has a stronger impact than Duox2
probably because it is expressed in the crypt of the gland. Drugs that have been effective in treating IBD, such as dexamethasone and
antibiotics, are likely mediated through suppression of NOX1 and DUOX2 gene expression.
Recent Publications
1.
Chu F F et al. (2004) Bacteria-induced intestinal cancer inmice deficient in both Gpx1 and Gpx2 genes. Cancer Res. 64:962-968.
2.
Hayes P et al. (2015) Defects in HADPH oxidase genes NOX1 and DUOX2 in very early onset inflammatory bowel disease. Cell
Mol. Gastroenterol. Hepatol. 1(5):489-502.
3.
Chu F F et al. (2017) Deficiency in Duox2 activity alleviates ileitis in GPx1- and GPx2-knockout mice without affecting
apoptosis incidence in the crypt epithelium. Redox Biology. 11:144-156.
4.
Liu H et al. (2017) Interleukin-4 and interleukin-13 increase NADPH oxidase 1-related proliferation of human colon cancer
cells. Oncotarget. 8(24):38113-38135.
Biography
Fong Fong Chu has her expertise in gastrointestinal diseases especially in inflammatory bowel disease (IBD). Her team has established a mouse model of IBD which is
very-early onset. These mice are deficient in two isoenzymes which reduce hydrogen peroxide named GPx1/2-double knockout (DKO). This model is a better model than
chemical-induced colitis models because it is not injury based and mimic closely to human IBD. She has built this model through 20 years of research and has identified
new targets for IBD therapy. She joined Beckman Research Institute of the City of Hope, Duarte CA USA (1987). She is currently associated with the Department of
Gastroenterology & Hepatology and the First Affiliated Hospital and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, Henan, P R
China since 2016.
fchu@coh.orgFong Fong Chu
The First Affiliated Hospital - HUST, P R China