The gastrointestinal epithelium functions as physical and innate immune barriers against commensal or pathogenic microbes.
NADPH oxidase 1 (Nox1) and
dual oxidase 2 (
Duox2), highly expressed in the colon, are suggested to play a potential role in host defense. Guinea-pig gastric pit cells and human colonic epithelial cells (T84 cells) express Nox1. With regard to activation of Nox1, the gastric epithelial cells are primed with
Helicobacter pylori lipopolysaccharide, whereas T84 cells preferentially use the
Toll-like receptor (TLR) 5, rather than TLR4, against Salmonella enteritidis
infection. Thus, gastric and colonic epithelial cells may use different TLR members to discern pathogenicities among bacteria, depending on their environments and to activate Nox1 appropriately for host defense. Nox1-derived
reactive oxygen species (ROS) have been implicated in the pathogenesis of
inflammation-associated
tumor development. The human stomach does not express Nox1. Helicobacter pylori
infection alone does not induce it, whereas Nox1 is specifically expressed in gastric
adenocarcinomas. In the human colon, Nox1 is differentiation-dependently expressed, and its expression is upregulated in
adenomas and well-differentiated
adenocarcinomas. Although Nox1 expression may not be directly linked to mitogenic activity, Nox1-derived ROS may exert a
cancer-promoting effect by increasing resistance to programmed cell death of
tumor cells.