Reference - Detail
| RRC ID | 42287 |
|---|---|
| Author | Nishimura H, Fujimoto A, Tamura N, Yajima T, Wajjwalku W, Yoshikai Y. |
| Title | A novel autoregulatory mechanism for transcriptional activation of the IL-15 gene by a nonsecretable isoform of IL-15 generated by alternative splicing. |
| Journal | 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. |
| Volume | 19(1) |
| Pages | 19-28 |
| Published | 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 |
| Times Cited | 39 |
| WOS Category | BIOLOGY BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY |
| Altmetric score |
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| The most frequently cited source | Patent(IFI CLAIMS) |
| Total number of mentions | 34 |
| Altmetric score changes over past 6months | 3.0 |
| Resource | |
| Human and Animal Cells | RAW 264(RCB0535) |