論文 - 詳細
| RRC ID | 5567 |
|---|---|
| 著者 | Martino ME, Olsen JC, Fulcher NB, Wolfgang MC, O'Neal WK, Ribeiro CM. |
| タイトル | Airway epithelial inflammation-induced endoplasmic reticulum Ca2+ store expansion is mediated by X-box binding protein-1. |
| ジャーナル | J Biol Chem |
| Abstract |
Inflamed cystic fibrosis (CF) human bronchial epithelia (HBE), or normal HBE exposed to supernatant from mucopurulent material (SMM) from CF airways, exhibit endoplasmic reticulum (ER)/Ca(2+) store expansion and amplified Ca(2+)-mediated inflammation. HBE inflammation triggers an unfolded protein response (UPR) coupled to mRNA splicing of X-box binding protein-1 (XBP-1). Because spliced XBP-1 (XBP-1s) promotes ER expansion in other cellular models, we hypothesized that XBP-1s is responsible for the ER/Ca(2+) store expansion in inflamed HBE. XBP-1s was increased in freshly isolated infected/inflamed CF in comparison with normal HBE. The link between airway epithelial inflammation, XBP-1s, and ER/Ca(2+) store expansion was then addressed in murine airways challenged with phosphate-buffered saline or Pseudomonas aeruginosa. P. aeruginosa-challenged mice exhibited airway epithelial ER/Ca(2+) store expansion, which correlated with airway inflammation. P. aeruginosa-induced airway inflammation triggered XBP-1s in ER stress-activated indicator (ERAI) mice. To evaluate the functional role of XBP-1s in airway inflammation linked to ER/Ca(2+) store expansion, control, XBP-1s, or dominant negative XBP-1 (DN-XBP-1) stably expressing 16HBE14o(-) cell lines were used. Studies with cells transfected with an unfolded protein response element (UPRE) luciferase reporter plasmid confirmed that the UPRE was activated or inhibited by expression of XBP-1s or DN-XBP-1, respectively. Expression of XBP-1s induced ER/Ca(2+) store expansion and potentiated bradykinin-increased interleukin (IL)-8 secretion, whereas expression of DN-XBP-1 inhibited bradykinin-dependent IL-8 secretion. In addition, expression of DN-XBP-1 blunted SMM-induced ER/Ca(2+) store expansion and SMM-induced IL-8 secretion. These findings suggest that, in inflamed HBE, XBP-1s is responsible for the ER/Ca(2+) store expansion that confers amplification of Ca(2+)-dependent inflammatory responses. |
| 巻・号 | 284(22) |
| ページ | 14904-13 |
| 公開日 | 2009-5-29 |
| DOI | 10.1074/jbc.M809180200 |
| PII | S0021-9258(19)82101-4 |
| PMID | 19321437 |
| PMC | PMC2685672 |
| MeSH | Alternative Splicing / genetics Animals Calcium / metabolism* Cell Polarity Cells, Cultured DNA-Binding Proteins / genetics DNA-Binding Proteins / metabolism* Endoplasmic Reticulum / metabolism* Epithelial Cells / metabolism Epithelial Cells / microbiology Epithelial Cells / pathology* Genes, Dominant Genetic Vectors / genetics Humans Inflammation / pathology* Interleukin-8 / metabolism Mice Protein Folding Pseudomonas aeruginosa RNA, Messenger / genetics RNA, Messenger / metabolism Regulatory Factor X Transcription Factors Respiratory System / microbiology Respiratory System / pathology* Signal Transduction Transcription Factors / genetics Transcription Factors / metabolism* X-Box Binding Protein 1 |
| IF | 4.238 |
| 引用数 | 50 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 1 |
| 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 | |
| 実験動物マウス | RBRC01099 |