Leptomycin B reduces matrix metalloproteinase-9 expression and suppresses cutaneous inflammation
Leptomycin B reduces matrix metalloproteinase-9 expression and suppresses cutaneous inflammation
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DOI：
10.1111/j.0022-202x.2004.23595.x
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发表时间：
2005-02-01
影响因子：
6.5
通讯作者：
Shinkai, H
中科院分区：
文献类型：
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作者：
Kobayashi, T;Shinkai, H
基质金属蛋白酶-9 （Matrix metalloproteinase-9, MMP-9）是一种明胶酶，在组织代谢，特别是炎症反应中起着多种作用，其编码基因的启动子区域已经报道了许多调控元件。Leptomycin B，它调节蛋白质的核细胞质运输。包括转录因子相关的，有可能发挥重要的生物学效应。在培养的角质形成细胞中添加leptomycin B对基质金属蛋白酶-2（另一种明胶酶）没有影响，但在高Ca2+或转化生长因子- β刺激分化以及肿瘤坏死因子-a或白细胞介素-la刺激炎症时，会导致MMP-9的选择性下调。这种下调依赖于MMP-9启动子中的多个调控元件，包括KRE-M9（我们最近发现的）和一个经典的12-o-十四烷醇-磷酸-13-乙酸酯响应元件。在小鼠皮肤外用leptomycin B也能有效抑制紫外线B照射后的炎症反应，包括MMP-9的表达。这些结果表明，应用leptomycin B和/或其衍生物可用于治疗许多炎症性疾病。
Matrix metalloproteinase-9 (MMP-9), a type of gelatinase, plays many roles in tissue metabolism, especially in inflammation, and many regulatory elements have been reported in the promoter region of its encoding gene. Leptomycin B, which regulates the nucleo-cytoplasmic trafficking of proteins. including transcription-factor-related ones, has the potential to exert important biological effects. The addition of leptomycin B to keratinocytes in culture had no effect on matrix metalloproteinase-2 (another gelatinase) but caused the selective down-regulation of MMP-9 during the stimulation of differentiation with high Ca2+ or transforming growth factor-beta, as well as during the stimulation of inflammation by tumor necrosis factor-a or interleukin-la. This down-regulation depended on multiple regulatory elements in the promoter of MMP-9 including KRE-M9 (which we have recently identified), and a classical 12-o-tetradecanoyl-phorbol-13-acetate-responsive element. The topical application of leptomycin B to murine skin also effectively suppressed inflammation, including MMP-9 expression, after ultraviolet B irradiation. These results suggest that the application of leptomycin B and/or its derivatives could be useful for treating many inflammatory conditions.