A novel autoregulatory mechanism for transcriptional activation of the IL-15 gene by a nonsecretable isoform of IL-15 generated by alternative splicing

Hitoshi Nishimura, Atsushi Fujimoto, Naoyuki Tamura, Toshiki Yajima, Worawidh Wajjwalku, Yasunobu Yoshikai

    研究成果: Contribution to journalArticle査読

    42 被引用数 (Scopus)

    抄録

    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 α 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 α (IL-15Rα). IL-15 promoter activity was suppressed in the transfected cells. Although nuclear factor-κB 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-15Rα. IL-15 was mainly colocalized with IL-15Rα at the cytoplasmic membrane of RAW264.7 cells, which had been cotransfected with normal IL-15, whereas nonsecretable IL-15 was colocalized with IL-15Rα in nucleus after cotransfection with alternative IL-15 and IL-15Rα. 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.

    本文言語英語
    ページ(範囲)19-28
    ページ数10
    ジャーナルFASEB Journal
    19
    1
    DOI
    出版ステータス出版済み - 1 2005

    All Science Journal Classification (ASJC) codes

    • バイオテクノロジー
    • 生化学
    • 分子生物学
    • 遺伝学

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