| First Author | Nishimura H | Year | 2005 |
| Journal | FASEB J | Volume | 19 |
| Issue | 1 | Pages | 19-28 |
| PubMed ID | 15629891 | Mgi Jnum | J:95444 |
| Mgi Id | MGI:3525993 | Doi | 10.1096/fj.04-2633com |
| Citation | Nishimura H, et al. (2005) A novel autoregulatory mechanism for transcriptional activation of the IL-15 gene by a nonsecretable isoform of IL-15 generated by alternative splicing. FASEB J 19(1):19-28 |
| abstractText | 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. |
