| RRC ID |
42287
|
| 著者 |
Nishimura H, Fujimoto A, Tamura N, Yajima T, Wajjwalku W, Yoshikai Y.
|
| タイトル |
A novel autoregulatory mechanism for transcriptional activation of the IL-15 gene by a nonsecretable isoform of IL-15 generated by alternative splicing.
|
| ジャーナル |
FASEB J
|
| Abstract |
There are several isoforms of interleukin (IL) -15 generated by alternating splicing. We reported previously that alternative IL-15 transgenic (Tg) mice expressing an IL-15 cDNA isoform encoding nonsecretable IL-15 protein had an impaired ability to produce IL-15. In this study, we found that expression of endogenous IL-15 mRNA but not tumor necrosis factor alpha mRNA was severely impaired in response to lipopolysaccharide, not only in macrophages from alternative IL-15 Tg mice but also in RAW264.7 cells that had been transfected with alternative IL-15 together with IL-15 receptor alpha (IL-15Ralpha). IL-15 promoter activity was suppressed in the transfected cells. Although nuclear factor-kappaB activation was not impaired, the binding activity of nuclear extracts to the interferon-stimulated response element of the IL-15 promoter region was reduced in RAW264.7 cells, which had been cotransfected with alternative IL-15 and IL-15Ralpha. IL-15 was mainly colocalized with IL-15Ralpha at the cytoplasmic membrane of RAW264.7 cells, which had been cotransfected with normal IL-15, whereas nonsecretable IL-15 was colocalized with IL-15Ralpha in nucleus after cotransfection with alternative IL-15 and IL-15Ralpha. These results suggest that nonsecretable IL-15 generated by alternative splicing suppresses further IL-15 gene transcription, implying a novel autocrine regulatory mechanism for cytokine gene expression by alternative splicing.
|
| 巻・号 |
19(1)
|
| ページ |
19-28
|
| 公開日 |
2005-1-1
|
| DOI |
10.1096/fj.04-2633com
|
| PII |
19/1/19
|
| PMID |
15629891
|
| MeSH |
Alternative Splicing / genetics*
Animals
Cell Line
DNA / metabolism
DNA-Binding Proteins / metabolism
Gene Expression Regulation / genetics
Homeostasis / genetics*
Interleukin-15 / genetics*
Interleukin-15 / metabolism*
Intracellular Space / chemistry
Macrophages / chemistry
Macrophages / metabolism
Mice
Promoter Regions, Genetic / genetics
Protein Isoforms / genetics
Protein Isoforms / metabolism
Receptors, Immunologic / metabolism
Receptors, Interleukin-15
Receptors, Interleukin-2
Signal Transduction / genetics
Toll-Like Receptor 4
Transcriptional Activation / genetics*
|
| IF |
4.966
|
| 引用数 |
39
|
|
WOS 分野
|
BIOLOGY
BIOCHEMISTRY & MOLECULAR BIOLOGY
CELL BIOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
RAW 264(RCB0535) |
