| RRC ID |
52065
|
| 著者 |
Ariyoshi W, Okinaga T, Chaweewannakorn W, Akifusa S, Nisihara T.
|
| タイトル |
Mechanisms involved in enhancement of matrix metalloproteinase-9 expression in macrophages by interleukin-33.
|
| ジャーナル |
J Cell Physiol
|
| Abstract |
Endothelial transmigration of macrophages is accomplished by matrix metalloproteinase (MMP)-induced degradation of the basement membrane and extracellular matrix components. Macrophages upregulate MMP-9 expression and secretion upon immunological challenges and require its activity for migration during inflammatory responses. Interleukin (IL)-33 is a recently discovered pro-inflammatory cytokine that belongs to the IL-1 family. The aim of this study was to elucidate the mechanisms underlying IL-33-induced MMP-9 expression in the mouse monocyte/macrophage line RAW264.7. IL-33 increased MMP-9 mRNA and protein expression in RAW264.7 cells. Blockage of IL-33-IL-33 receptor (ST2L) binding suppressed IL-33-mediated induction of MMP-9. IL-33 induced phosphorylation and nuclear translocation of extracellular signal-regulated kinase 1/2 (ERK1/2) and nuclear factor-kappa B (NF-κB). Chromatin immunoprecipitation indicated that IL-33 increased c-fos recruitment to the MMP-9 promoter. Reporter assay findings also revealed that IL-33 stimulated the transcriptional activity of activator protein 1 (AP-1). Pre-treatment of the cells with a specific inhibitor of ERK1/2 and NF-κB attenuated the IL-33-induced activation of AP-1 subunits, transcriptional activity of AP-1, and expression of MMP-9. We also demonstrated that ERK-dependent activation of cAMP response element binding protein (CREB) is a key step for AP-1 activation by IL-33. These results indicate an essential role of ERK/CREB and NF-κB cascades in the induction of MMP-9 in monocytes/macrophages through AP-1 activation.
|
| 巻・号 |
232(12)
|
| ページ |
3481-3495
|
| 公開日 |
2017-12-1
|
| DOI |
10.1002/jcp.25809
|
| PMID |
28105703
|
| MeSH |
Animals
Cyclic AMP Response Element-Binding Protein / genetics
Cyclic AMP Response Element-Binding Protein / metabolism
Dose-Response Relationship, Drug
Extracellular Signal-Regulated MAP Kinases / metabolism
Interleukin-33 / pharmacology*
Macrophages / drug effects*
Macrophages / enzymology
Matrix Metalloproteinase 9 / genetics
Matrix Metalloproteinase 9 / metabolism*
Mice
NF-kappa B / metabolism
Phosphorylation
Promoter Regions, Genetic
Protein Binding
RAW 264.7 Cells
RNA Interference
Receptors, Interleukin-1 / agonists
Receptors, Interleukin-1 / genetics
Receptors, Interleukin-1 / metabolism
Signal Transduction / drug effects
Time Factors
Transcription Factor AP-1 / genetics
Transcription Factor AP-1 / metabolism
Transcription, Genetic
Transcriptional Activation
Transendothelial and Transepithelial Migration / drug effects
Transfection
Tumor Necrosis Factor-alpha / genetics
Tumor Necrosis Factor-alpha / metabolism
Up-Regulation
|
| IF |
4.522
|
| 引用数 |
10
|
| リソース情報 |
| ヒト・動物細胞 |
RAW 264(RCB0535) |
