Toll-like receptor 4 regulates gastric pit cell responses to Helicobacter pylori infection.
Gastric pit cells express mitogen oxidase1 (Mox1) and essential components for the phagocyte NADPH oxidase (p67-, p47-, p40-, and p22-phoxes). Helicobacter pylori (Hp) lipopolysaccharide (LPS) is a potent up-regulator of the Mox 1 oxidase. In this study, we examined the expression levels of several key members of the Toll-like receptor (TLR) family in primary cultures of guinea pig gastric pit cells. These cells expressed the TLR4 mRNA. Immunoblot analysis and immunofluorescence histochemistry with an anti-TLR4 antibody showed that gastric pit cells possessed significant amounts of TLR4 protein preferentially on the plasma membrane. In contrast, the cells did not express the TLR2 and TLR9 transcripts and did not contain detectable amounts of TLR2 protein. Neither peptidoglycan from Staphylococcus aureus nor Hp DNA with the CpG motif up-regulated Mox1 oxidase activity. Hp LPS activated nuclear factor-kappa B in association with the expression of cyclooxygenase II and tumor necrosis factor alpha transcripts. These findings suggest that TLR4 may play a crucial role in the initiation of inflammatory responses of gastric pit cells against 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
Kawai
T
T
Nikawa
T
T
Kishi
K
K
Rokutan
K
K
D000818:Animals; D018899:CpG Islands; D051546:Cyclooxygenase 2; D029721:Drosophila Proteins; D005753:Gastric Mucosa / Q000166:cytology / Q000276:immunology* / Q000382:microbiology; D005756:Gastritis / Q000276:immunology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006168:Guinea Pigs; D016481:Helicobacter Infections / Q000276:immunology*; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000502:physiology*; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism; D019255:NADPH Oxidases; D016328:NF-kappa B / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D010457:Peptidoglycan / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D011956:Receptors, Cell Surface / Q000502:physiology*; D013211:Staphylococcus aureus / Q000737:chemistry; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics
D029721:Drosophila Proteins; D007527:Isoenzymes; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D010457:Peptidoglycan; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D009247:NADH, NADPH Oxidoreductases; D019255:NADPH Oxidases; C022709:superoxide-forming enzyme; D010100:Oxygen