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

概要

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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.Recently, much attention has been paid to leptomycin B (LMB), a modulator for trafficking a variety of transcription-related proteins from nucleus to cytoplasm.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.Topical applications of LMB on the murine skin after UVB irradiation prevented the skin from the dyskeratosis and from the infiltrates of inflammatory cells.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.
日本炎症・再生医学会の論文
2004-09-25