Fong-Fong Chu
The First Affiliated Hospital - HUST, P R China
Title: Reactive oxygen species generated by NADPH oxidase-1 and Dual oxidase-2 contribute to inflammatory bowel disease
Biography
Biography: Fong-Fong Chu
Abstract
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-earlyonset 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.