Helicobacter pylori activates Toll-like receptor 4 expression in gastrointestinal epithelial cells.
Helicobacter pylori activates the transcription factor NF-kappaB, leading to proinflammatory cytokine production by gastric epithelial cells. However, the receptors for the initial bacterial interaction with host cells which activate downstream signaling events have not been completely defined. Recently, it has been shown that microbial components activate Toll-like receptors (TLRs), thereby leading to AP-1- and NF-kappaB-dependent transcription and resulting in the production of proinflammatory cytokines. The aim of this study was to determine whether H. pylori activates TLR4. Reverse transcription-PCR showed that both type I and type II H. pylori clinical isolates induced TLR4 mRNA expression in AGS cells compared with that by uninfected controls. H. pylori upregulated TLR4 protein expression in two gastric epithelial cell lines (AGS and MKN45) and one intestinal epithelial cell line (T84). Monoclonal TLR4 antibody inhibited lipopolysaccharide-induced interleukin-8 secretion from THP-1 macrophages but not from gastric epithelial cells infected with H. pylori. H. pylori demonstrated increased adherence to CHO TLR4-transfected cells compared with that to both CHO TLR2-transfected and nontransfected CHO cells (P < 0.01). These results indicate that H. pylori activates TLR4 expression in epithelial cells and that TLR4 can serve as a receptor for H. pylori binding.
Su
Bin
B
Research Institute, Hospital for Sick Children, Department of Paediatrics, University of Toronto, Ontario, Canada.
Ceponis
Peter J M
PJ
Lebel
Sylvie
S
Huynh
Hien
H
Sherman
Philip M
PM
D000818:Animals; D016466:CHO Cells; D002460:Cell Line; D018925:Chemokines / Q000378:metabolism; D006224:Cricetinae; D005753:Gastric Mucosa / Q000378:metabolism*; D006031:Glycosylation; D016480:Helicobacter pylori / Q000502:physiology*; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism*; D018950:Lipopolysaccharide Receptors / Q000502:physiology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D011956:Receptors, Cell Surface / Q000096:biosynthesis* / Q000235:genetics; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D015854:Up-Regulation
D018925:Chemokines; D016209:Interleukin-8; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors