ダイチョウ ジョウヒ サイボウ ニ ハツゲン スル NADPH oxidase1 Nox1 ノ ブンシ トクセイ

NADPH oxidase 1 (Nox1) is an isozyme of gp91-phox predominantly expressed in the human colon. In this study, we have established primary cultures of guinea pig large intestinal epithelial cells (LIEC). A great majority of the cultured cells (>90%) was surface mucous cells containing periodic acid-Schiff reaction-positive granules. Vimentin-positive fibroblasts were <1%, and macrophages were not contaminated. LIEC spontaneously produced superoxide anion (O2 －) at about 160 nmol/mg protein/h. O2 －-dependent formation of blue formazan particles from nitroblue tetrazolium was observed only on surface of mucous-producing cells, and these cells expressed Nox1 protein at plasma membrane and in the cytoplasm. They expressed p67-phox, p22-phox, and rac1, but not gp91-phox, p47-phox, p40-phox, and rac 2. Immunohistochemistry showed that Nox1, p 67-phox, and p 22-phox were predominantly expressed in surface mucous cells of human and guinea pig colonic mucosa. Human colon cancer cell lines (Caco2, T84, and HT29 cells) expressed Nox1, p22-phox, and rac1, but not the other NADPH components. These cells secreted O2 － at <5 nmol/mg protein/h. Caco2 cells possessed Toll-like receptor 5, and flagellin (FliC) from Salmonella enteritidis phosphorylated transforming growth factor-β-activated kinase 1 (TAK1) and TAK1-binding protein 1, and significantly up-regulated O2 － production. These results suggest that Nox1 expressed in colonic epithelial cells may regulate interactions between pathogenic bacteria and epithelial cells for host defense