Helicobacter pylori lipopolysaccharide from type I, but not type II strains, stimulates apoptosis of cultured gastric mucosal cells.
The cag pathogenicity island (cag PAI) genes are a major determinant of virulence of Helicobacter pylori (Hp). Lipopolysaccharide (LPS) purified from the cag PAI-positive (type I) strains induced apoptosis of primary cultures of guinea pig gastric mucosal cells. Lipid A catalyzed this apoptosis. These cells expressed the Toll-like receptor 4 (TLR4) mRNA and its protein, and type I Hp LPS phosphorylated transforming growth factor beta-activated kinase 1 (TAK1) and TAK1-binding protein 1 (TAB1) in association with up-regulation of the TLR4 expressions, suggesting that type I Hp LPS evoked distinct TLR4 signaling. In contrast, Hp LPS from type II strains with complete or partial deletion of the cag PAI genes did not phosphorylate TAK1 and TAB1 and failed to induce apoptosis. Accelerated apoptosis of gastric epithelial cells is one of the important events relevant to chronic, atrophic gastritis caused by Hp infection. The difference in proapoptotic action of LPS between the type I and II strains may support an important role of the cag PAI genes in the pathogenesis of gastric lesions caused by Hp infection.
Kawahara
T
T
Department of Nutritional Physiology, University of Tokushima School of Medicine, Kuramoto-cho, Tokushima 770-8503, Japan.
Kuwano
Y
Y
Teshima-Kondo
S
S
Sugiyama
T
T
Kawai
T
T
Nikawa
T
T
Kishi
K
K
Rokutan
K
K
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000942:Antigens, Bacterial; D017209:Apoptosis / Q000187:drug effects*; D001284:Atrophy; D001426:Bacterial Proteins / Q000235:genetics; D002352:Carrier Proteins / Q000378:metabolism; D029721:Drosophila Proteins; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects* / Q000473:pathology; D005756:Gastritis / Q000382:microbiology / Q000473:pathology; D005838:Genotype; D006168:Guinea Pigs; D016481:Helicobacter Infections / Q000382:microbiology / Q000473:pathology; D016480:Helicobacter pylori / Q000737:chemistry* / Q000145:classification / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008050:Lipid A / Q000302:isolation & purification / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000302:isolation & purification / Q000494:pharmacology*; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics; D010766:Phosphorylation / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000235:genetics; D015398:Signal Transduction; D013268:Stimulation, Chemical; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D000099151:MAP Kinase Kinase Kinase 7
D048868:Adaptor Proteins, Signal Transducing; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D002352:Carrier Proteins; D029721:Drosophila Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008050:Lipid A; D008070:Lipopolysaccharides; D020930:MAP Kinase Kinase Kinases; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D000099151:MAP Kinase Kinase Kinase 7; C103937:PicB protein, Helicobacter pylori; C099510:TAB1 protein, MAPKKK activator, vertebrate; C486300:TAB1 protein, human; C495345:TLR4 protein, human; C074689:VacA protein, Helicobacter pylori; C080866:cagA protein, Helicobacter pylori; C442865:lipopolysaccharide, Helicobacter pylori