Type I Helicobacter pylori lipopolysaccharide stimulates toll-like receptor 4 and activates mitogen oxidase 1 in gastric pit cells

Guinea pig gastric pit cells express an isozyme of gp91-phox, mitogen oxida se 1 (Mox1), and essential components for the phagocyte NADPH oxidase (p67- , p47-, p40-, and p22-phox). Helicobacter pylori lipopolysaccharide (LPS) a nd Escherichia coli LPS have been shown to function as potent activators fo r the Mox1 oxidase, These cells spontaneously secreted about 10 nmol of sup eroxide anion (O-2(-))/mg of protein/h under LPS-free conditions. They expr essed the mRNA and protein of Toll-like receptor 4 (TLR4) but not those of TLR2, LPS from type I H. pylori at 2.1 endotoxin units/ml or higher stimula ted TLR4-mediated phosphorylations of transforming growth factor P-activate d kinase 1 and its binding protein 1 induced TLR4 and p67-phox and up-regul ated O-2(-) production 10-fold, In contrast, none of these events occurred with H. pylori LPS from complete or partial deletion mutants of the cag pat hogenicity island. Lipid A was confirmed to be a bioactive component for th e priming effects, while removal of bisphosphates from lipid A completely e liminated the effects, suggesting the importance of the phosphorylation pat tern besides the acylation pattern for the bioactivity, H, pylori LPS is ge nerally accepted as having low toxicity; however, our results suggest that type I H, pylori lipid A may be a potent stimulator for innate immune respo nses of gastric mucosa by stimulating the TLR4 cascade and Mox1 oxidase in pit cells.