| RRC ID |
63410
|
| 著者 |
Asano N, Imatani A, Watanabe T, Fushiya J, Kondo Y, Jin X, Ara N, Uno K, Iijima K, Koike T, Strober W, Shimosegawa T.
|
| タイトル |
Cdx2 Expression and Intestinal Metaplasia Induced by H. pylori Infection of Gastric Cells Is Regulated by NOD1-Mediated Innate Immune Responses.
|
| ジャーナル |
Cancer Res
|
| Abstract |
Chronic infection with the bacterial Helicobacter pylori is a major cause of gastric and duodenal ulcer disease, gastric mucosal atrophy, and cancer. H. pylori-induced expression of the intestinal epithelial-specific transcription factor caudal-related homeobox 2 (Cdx2) contributes to intestinal metaplasia, a precursor event to gastric cancer. Given a role for the bacterial pattern recognition molecule nucleotide-binding oligomerization domain 1 (NOD1) in the innate immune response to bacterial infection, we investigated mechanisms used by NOD1 to regulate H. pylori infection and its propensity towards the development of intestinal metaplasia. We found that Cdx2 was induced by H. pylori infection in both normal and neoplastic gastric epithelial cells in a manner that was inversely related to NOD1 signaling. Mechanistic investigations revealed that Cdx2 induction relied upon activation of NF-κB but was suppressed by NOD1-mediated activation of TRAF3, a negative regulator of NF-κB. In vivo, prolonged infection of NOD1-deficient mice with H. pylori led to increased Cdx2 expression and intestinal metaplasia. Furthermore, gastric epithelial cells from these mice exhibited increased nuclear expression of the NF-κB p65 subunit and decreased expression of TRAF3. Overall, our findings illuminated a role for NOD1 signaling in attenuating H. pylori-induced Cdx2 expression in gastric epithelial cells, suggesting a rationale to augment NOD1 signaling in H. pylori-infected patients to limit their risks of accumulating precancerous gastric lesions.
|
| 巻・号 |
76(5)
|
| ページ |
1135-45
|
| 公開日 |
2016-3-1
|
| DOI |
10.1158/0008-5472.CAN-15-2272
|
| PII |
0008-5472.CAN-15-2272
|
| PMID |
26759244
|
| PMC |
PMC4799656
|
| MeSH |
Animals
CDX2 Transcription Factor
Cell Line, Tumor
Gastric Mucosa / metabolism
Gastric Mucosa / pathology*
Helicobacter Infections / complications*
Helicobacter Infections / metabolism
Helicobacter pylori*
Homeodomain Proteins / genetics
Homeodomain Proteins / physiology*
Humans
Immunity, Innate
Male
Metaplasia
Mice, Inbred C57BL
NF-kappa B / physiology
Nod1 Signaling Adaptor Protein / physiology*
Promoter Regions, Genetic
Signal Transduction
TNF Receptor-Associated Factor 3 / physiology
Transcription Factors / genetics
Transcription Factors / physiology*
|
| IF |
9.727
|
| リソース情報 |
| ヒト・動物細胞 |
GSM06(RCB1779) |
