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 oxidase 1 (Mox1), and essential components for the phagocyte NADPH oxidase (p67-, p47-, p40-, and p22-phox). Helicobacter pylori lipopolysaccharide (LPS) and Escherichia coli LPS have been shown to function as potent activators for the Mox1 oxidase. These cells spontaneously secreted about 10 nmol of superoxide anion (O(2)(-))/mg of protein/h under LPS-free conditions. They expressed 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 stimulated TLR4-mediated phosphorylations of transforming growth factor beta-activated kinase 1 and its binding protein 1 induced TLR4 and p67-phox and up-regulated 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 pathogenicity island. Lipid A was confirmed to be a bioactive component for the priming effects, while removal of bisphosphates from lipid A completely eliminated the effects, suggesting the importance of the phosphorylation pattern besides the acylation pattern for the bioactivity. H. pylori LPS is generally accepted as having low toxicity; however, our results suggest that type I H. pylori lipid A may be a potent stimulator for innate immune responses of gastric mucosa by stimulating the TLR4 cascade and Mox1 oxidase in pit cells.
Kawahara
T
T
Department of Nutritional Physiology, School of Medicine, University of Tokushima, Tokushima 770-8503, Japan.
Teshima
S
S
Oka
A
A
Sugiyama
T
T
Kishi
K
K
Rokutan
K
K
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D002478:Cells, Cultured; D029721:Drosophila Proteins; D004789:Enzyme Activation; D005753:Gastric Mucosa / Q000166:cytology / Q000378:metabolism*; D015870:Gene Expression; D006168:Guinea Pigs; D016480:Helicobacter pylori / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D007527:Isoenzymes / Q000378:metabolism; D008070:Lipopolysaccharides / Q000378:metabolism*; D020930:MAP Kinase Kinase Kinases; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism*; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000378:metabolism; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D000099151:MAP Kinase Kinase Kinase 7
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D029721:Drosophila Proteins; D047908:Intracellular Signaling Peptides and Proteins; D007527:Isoenzymes; D008070:Lipopolysaccharides; D020930:MAP Kinase Kinase Kinases; D008562:Membrane Glycoproteins; D009247:NADH, NADPH Oxidoreductases; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; D011494:Protein Kinases; D011956:Receptors, Cell Surface; D013481:Superoxides; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D000099151:MAP Kinase Kinase Kinase 7; C099510:TAB1 protein, MAPKKK activator, vertebrate; C486300:TAB1 protein, human; C495342:TLR2 protein, human; C495345:TLR4 protein, human; C056558:CYBB protein, human; C022709:superoxide-forming enzyme