論文 - 詳細
| RRC ID | 62181 |
|---|---|
| 著者 | Chang YJ, Wu MS, Lin JT, Chen CC. |
| タイトル | Helicobacter pylori-Induced invasion and angiogenesis of gastric cells is mediated by cyclooxygenase-2 induction through TLR2/TLR9 and promoter regulation. |
| ジャーナル | J Immunol |
| Abstract |
Cyclooxygenase-2 (COX-2) plays a crucial role in Helicobacter pylori-associated gastric cancer. In this study, we report that H. pylori-induced COX-2 expression enhances the cancer cell invasion and angiogenesis via TLR2 and TLR9, which can be attenuated by the specific COX-2 inhibitor NS398 or celecoxib. The cAMP response element (CRE) and AP1 sites, but not kappaB on the COX-2 promoter, are involved in MAPKs-regulated COX-2 expression. Differential bindings of the CREB-1, ATF-2, c-jun to the CRE site, and the c-fos, c-jun, ATF-2 to the AP1 site are demonstrated by DNA affinity protein-binding, supershift, and chromatin immunoprecipitation assays. Activations of these transcription factors were attenuated by different MAPKs inhibitors. The mutants of TLR2, TLR9, or MAPKs inhibited H. pylori-induced COX-2 promoter, CRE, and AP-1 activities. MAPKs inhibitors attenuated the H. pylori-induced COX-2 mRNA and protein expressions. These results indicate that H. pylori acts through TLR2 and TLR9 to activate MAPKs, especially p38, and their downstream transcription factors (CREB-1, ATF-2, c-jun, and c-fos), resulting in the activations of CRE and AP-1 on the COX-2 promoter. These intracellular networks drive the COX-2-dependent PGE2 release and contribute to cell invasion and angiogenesis. |
| 巻・号 | 175(12) |
| ページ | 8242-52 |
| 公開日 | 2005-12-15 |
| DOI | 10.4049/jimmunol.175.12.8242 |
| PII | 175/12/8242 |
| PMID | 16339564 |
| MeSH | Cell Line, Tumor Cyclooxygenase 2 / genetics Cyclooxygenase 2 / physiology* Dinoprostone / metabolism Helicobacter pylori* Humans Membrane Proteins / genetics Membrane Proteins / physiology* Neoplasm Invasiveness / pathology* Neovascularization, Pathologic / enzymology Neovascularization, Pathologic / virology* Promoter Regions, Genetic Stomach Neoplasms / pathology* Stomach Neoplasms / virology* Toll-Like Receptor 2 / physiology Toll-Like Receptor 9 / physiology Transcription Factor AP-1 / metabolism Transcription Factors / metabolism |
| IF | 4.886 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 各媒体での言及数の合計 | 0 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | MKN45(RCB1001) |