Toll‐like Receptor 2‐Mediated Gene Expression in Epithelial Cells During <i>Helicobacter pylori</i> Infection

Ding, Song‐Ze; Torok, Anastasia M.; Smith, Michael F.; Goldberg, Joanna B.

doi:10.1111/j.1523-5378.2005.00311.x

Cited by 49 publications

(54 citation statements)

References 52 publications

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“…Interestingly, Ikeda et al (2007) reported that pre-incubation of rat biliary epithelial cells with anti-TLR4 or anti-TLR2 antibodies downregulated MUC2 expression induced by LPS. In contrast, TLR2 and bacterial components induced expression of MUC2 in cultured gastric epithelial cell lines and were activated by nuclear factor (NF)-kB (Ding et al, 2005;Ikeda et al, 2007). All of these results, including ours, suggest that G. seoi antigen induces MUC2 expression via the activation of the TLR pathways in human IECs.…”

Section: Discussioncontrasting

confidence: 40%

Toll-Like Receptor 2 andMuc2Expression on Human Intestinal Epithelial Cells by Gymnophalloides seoi Adult Antigen

Lee¹,

Guk²,

Chai³

2010

Journal of Parasitology

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Section: Discussioncontrasting

confidence: 40%

Toll-Like Receptor 2 andMuc2Expression on Human Intestinal Epithelial Cells by Gymnophalloides seoi Adult Antigen

Lee¹,

Guk²,

Chai³

2010

Journal of Parasitology

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“…Ding et al also reported that H. pylori activates MAP kinase pathways, and treatment with an ERK1/2 inhibitor resulted in accumulation of cells at the G 0 /G 1 stage (6). Earlier, Ding et al had used a microarray to screen genes induced by H. pylori and tested the dependence of the induction on TLR2, using HEK cells with or without the transfection of TLR2 expression plasmid (7). Genes upregulated in a TLR2-dependent way during H. pylori infection were IL-8, growth-related oncogenes, and molecules contributing to NF-B pathways.…”

Section: Discussionmentioning

confidence: 99%

Helicobacter pylori Lipopolysaccharides Upregulate Toll-Like Receptor 4 Expression and Proliferation of Gastric Epithelial Cells via the MEK1/2-ERK1/2 Mitogen-Activated Protein Kinase Pathway

et al. 2010

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Helicobacter pylori is recognized as an etiological agent of gastroduodenal diseases. H. pylori produces various toxic substances, including lipopolysaccharide (LPS). However, H. pylori LPS exhibits extremely weakly endotoxic activity compared to the typical LPS, such as that produced by Escherichia coli, which acts through Toll-like receptor 4 (TLR4) to induce inflammatory molecules. The gastric epithelial cell lines MKN28 and MKN45 express TLR4 at very low levels, so they show very weak interleukin-8 (IL-8) production in response to E. coli LPS, but pretreatment with H. pylori LPS markedly enhanced IL-8 production induced by E. coli LPS by upregulating TLR4 via TLR2 and the MEK1/2-ERK1/2 pathway. The transcription factor NF-Y was activated by this signal and promoted transcription of the tlr4 gene. These MEK1/2-ERK1/2 signal-mediated activities were more potently activated by LPS carrying a weakly antigenic epitope, which is frequently found in gastric cancers, than by LPS carrying a highly antigenic epitope, which is associated with chronic gastritis. H. pylori LPS also augmented the proliferation rate of gastric epithelial cells via the MEK1/2-ERK1/2 pathway. H. pylori LPS may be a pathogenic factor causing gastric tumors by enhancing cell proliferation and inflammation via the MEK1/2-ERK1/2 mitogenactivated protein kinase cascade in gastric epithelial cells.

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“…2,[4][5][6] For example, CDX2 expression was reportedly upregulated in cultured epithelial cells when they were infected with bacteria, and interactions of TLR with microbial components are involved in the regulation of MUC expression. [30][31][32][33][34][35] Therefore, bacterial components in bile may induce CDX2 expression and then aberrant MUC2 expression in the ducts.…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, preincubation with anti-TLR4 antibody or anti-TLR2 antibody downregulated CDX2 and MUC2 expression in BECs induced by LPS (a ligand for TLR4) or Pam3 (a ligand for TLR2), respectively, Interaction of TLR with PAMPs is known to activate intracellular signals followed by NF-kB translocation and the synthesis of molecules including inflammatory cytokines. 24,35 The involvement of TLR2 and/or TLR4 in Helicobacter pylori infections has been revealed in cultured gastric epithelial cell lines, 33,34 in which MUC2 was induced to express by TLR2/ bacterial components and the activation of NF-kB. 3,31,32 PAMPs-induced CDX2 and MUC2 overexpression via an NF-kB pathway located downstream of TLRs.…”

Section: Intestinal Metaplasia Of Bile Ducts H Ikeda Et Almentioning

confidence: 99%

Interaction of Toll-like receptors with bacterial components induces expression of CDX2 and MUC2 in rat biliary epithelium in vivo and in culture

Ikeda

Sasaki

Ishikawa

et al. 2007

Laboratory Investigation

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The mechanism of transformation of biliary epithelium leading to intestinal metaplasia, which is significantly involved in biliary diseases, remains unclear. CDX2, an intestine-specific transcription factor, is thought to regulate intestinal mucin MUC2 (mucus core protein) expression. We took advantage of polycystic kidney (PCK) rats as a model of chronic suppurative cholangitis with intestinal metaplasia and of cultured biliary epithelial cells (BECs) from PCK rats to clarify the causal relation between bacterial components such as pathogen-associated molecular patterns (PAMPs) and the development of intestinal metaplasia of bile ducts. Histological, immunohistochemical, and in situ hybridization studies were conducted in PCK rat livers. In cultured BECs, CDX2 and MUC2 were expressed following treatment with PAMPs and inhibitors (anti-Toll-like receptor (TLR)2/TLR4 antibody, nuclear factor-kB (NF-kB) inhibitor MG132). Chronic suppurative cholangitis with intestinal metaplasia developed as the PCK rats aged, and intestinal metaplasia and aberrant CDX2 and MUC2 expression developed in parallel. Intraluminal bacteria and the expression of TLR2 and TLR4 in BECs were demonstrated in the bile ducts, showing chronic suppurative cholangitis. In cultured BECs, treatment with PAMPs induced upregulation of CDX2 and MUC2 expression, and this effect was abolished by pretreatment with anti-TLR2 and anti-TLR4 antibody and MG132. A knockdown of CDX2 by CDX2 small interfering RNA inhibited MUC2 expression in cultured BECs induced by PAMPs, and transfection of CDX2 expression vector induced MUC2 expression. In conclusion, bacterial components may induce upregulation of the CDX2 expression followed by MUC2 expression via TLR and the NF-kB system in cultured BECs, and could be related to the development of intestinal metaplasia of the bile ducts. Intestinal metaplasia associated with the aberrant expression of MUC2 1-4 is reportedly involved in tumorigenesis in several organs. Recent studies revealed that CDX2, a caudalrelated homeobox gene encoding an intestine-specific transcription factor, is a regulatory factor of intestinal development and expression of intestinal genes including MUC2 and is involved in intestinal metaplasia. 2,4,5-8 CDX2-dependent intestinal metaplasia is noted in Barrett's esophagus with MUC2 expression, and bile acid and chronic acid exposure have been reported to induce CDX2 expression. 2,[4][5][6]8,9 Intestinal metaplasia is also involved in the pathogenesis of biliary diseases. For example, in chronic cholangitis such as hepatolithiasis, intestinal metaplasia with goblet cells occurs, and MUC2 is aberrantly expressed in goblet cells colocalized with CDX2.

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Toll‐like Receptor 2‐Mediated Gene Expression in Epithelial Cells During Helicobacter pylori Infection

Cited by 49 publications

References 52 publications

Toll-Like Receptor 2 andMuc2Expression on Human Intestinal Epithelial Cells by Gymnophalloides seoi Adult Antigen

Toll-Like Receptor 2 andMuc2Expression on Human Intestinal Epithelial Cells by Gymnophalloides seoi Adult Antigen

Helicobacter pylori Lipopolysaccharides Upregulate Toll-Like Receptor 4 Expression and Proliferation of Gastric Epithelial Cells via the MEK1/2-ERK1/2 Mitogen-Activated Protein Kinase Pathway

Interaction of Toll-like receptors with bacterial components induces expression of CDX2 and MUC2 in rat biliary epithelium in vivo and in culture

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