Aim: To decipher DUOX2 expression and function in intestinal inflammation.
DUOX2 mRNA expression in the non-inflamed small and large intestine of IBD patients was increased (30 fold, p<0.05). This was further augmented in inflamed IBD tissues (≥ 150 fold, p<0.001). Decrease in microbial taxa diversity was observed in fecal samples from IBD patients with inactive disease compared to normal controls (p<0.004). Further decrease was noticed in fecal samples from IBD patients with active disease (p<0.0001). DUOX2 expression by epithelial cell lines significantly increased in response to inflammatory cytokines (IL-1b, TNF-a, IFN-g, IFN-b) (≥300 fold increase, p<0.001) and to fecal extracts derived from patients with active IBD (≥10 fold increase, p<0.001). ROS production increased in response to fecal extracts derived from patients with active IBD (3 fold, p<0.001) but not in response to inflammatory cytokines alone.
Increase in DUOX2 mRNA expression and decrease in microbial taxa diversity in fecal samples correlated with IBD activity. DUOX2 expression in epithelial cells is increased in response to inflammatory stimuli and to fecal extracts derived from patients with active IBD. In contrast, ROS production increased only in response to fecal extracts. Thus DUOX2 increased expression and aberrant function are affected by inflammatory stimuli and intestinal microorganisms, and may have a role in further augmenting intestinal inflammation in IBD.