Role of matrix metalloproteinase-9 expression on cutaneous inflammation: Possible treatment by leptomycin B application

  • Kobayashi Takashi
    Department of Dermatology/Clinical Biology of Extracellular Matrix (F7), Chiba University School of Medicine

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  • 皮膚の炎症性疾患におけるmatrix metalloproteinase‐9の役割―Leptomycin B投与による治療の可能性について―

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Abstract

Matrix metalloproteinase-9 has been suggested to play many roles in the inflammation including bullous disease, tumor invasion and metastasis, ultraviolet (UV) B-irradiated dermatosis, and dyskeratosis. We previously showed the upregulation of MMP-9 transcripts due to KRE-M9 element in the MMP-9 promoter in the differentiation of keratinocytes.<BR>Recently, much attention has been paid to leptomycin B (LMB), a modulator for trafficking a variety of transcription-related proteins from nucleus to cytoplasm.<BR>By the addition of LMB for kertinocytes in culture, MMP-9 secretions were reduced in comparison with MMP-2, even in the up-regulations of MMP-9 expression in high calcium or in the addition of transforming growth factor-β, both of which cause the differentiation of keratinocytes, and in the additions of tumor necrosis factor-α or interleukin-1α, inflammatory and apoptotic cytokines. In addition, KRE-M9 as well as other elements including 12-o-tetradecanoyl-o-phorbol-13-acetate responsive element was shown to be responsible for the reduced MMP-9 transcription by LMB.<BR>Topical applications of LMB on the murine skin after UVB irradiation prevented the skin from the dyskeratosis and from the infiltrates of inflammatory cells.<BR>These results indicate that the applications of LMB and of its derivatives could be a useful remedy for many pathological conditions in which MMP-9 are involved.

Journal

  • Ensho Saisei

    Ensho Saisei 24 (5), 578-583, 2004

    The Japanese Society of Inflammation and Regeneration

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