Interferon-gamma coordinately upregulates matrix metalloprotease (MMP)-1 and MMP-3, but not tissue inhibitor of metalloproteases (TIMP), expression in cultured keratinocytes.
Interferon-gamma coordinately upregulates matrix metalloprotease (MMP)-1 and MMP-3, but not tissue inhibitor of metalloproteases (TIMP), expression in cultured keratinocytes.
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干扰素-γ 协同上调培养的角质形成细胞中基质金属蛋白酶 (MMP)-1 和 MMP-3 的表达，但不上调金属蛋白酶组织抑制剂 (TIMP) 的表达。
DOI：
10.1111/1523-1747.ep12665857
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发表时间：
1995
期刊：
影响因子：
--
通讯作者：
Uitto,J
中科院分区：
文献类型：
--
作者：
Tamai,K;Ishikawa,H;Mauviel,A;Uitto,J
基质金属蛋白酶（MMP）是降解细胞外基质成分的蛋白水解酶家族。其活性被金属蛋白酶组织抑制剂（TIMP）抑制。已有研究表明，多种细胞因子可调节MMP和TIMP基因表达。在这项研究中，我们证明干扰素-γ协同上调培养的角质形成细胞中MMP-1（间质胶原酶）和MMP-3（基质溶解素-1）基因表达，如在mRNA稳态水平所测定的，并且这种作用依赖于正在进行的蛋白质合成。相反，对TIMP-1基因表达没有影响。Western分析也证实IFN-γ在蛋白水平上增强MMP-1的表达。用MMP-1和MMP-3启动子/报告基因构建体瞬时转染显示对IFN-γ无应答，而用该细胞因子孵育角质形成细胞似乎可稳定MMP-1 mRNA，导致转录物周转减少。这些数据表明，IFN-γ在转录后水平增强MMP基因表达，IFN-γ改变MMP表达而不伴随TIMP基因表达的影响，可能导致这些蛋白酶及其抑制剂之间的失衡，并且增强的蛋白水解活性可能在涉及炎症过程的皮肤组织重塑中发挥作用，例如伤口愈合。
Matrix metalloproteases (MMP) constitute a family of proteolytic enzymes degrading extracellular matrix components. Their activity is inhibited by tissue inhibitors of metalloproteases (TIMP). Previous studies have demonstrated that various cytokines can modulate MMP and TIMP gene expression. In this study, we demonstrate that interferon-γ coordinately upregulates MMP-1 (interstitial collagenase) and MMP-3 (stromelysin-1) gene expression in cultured keratinocytes, as determined at the mRNA steady- state levels, and this effect is dependent on on-going protein synthesis. In contrast, there was no effect on TIMP-1 gene expression. Enhanced MMP-1 expression by IFN-γ was also demonstrated at the protein level by Western analysis. Transient transfections with MMP-1 and MMP-3 promoter/reporter gene constructs revealed no response to IFN-γ, whereas incubation of keratinocytes with this cytokine appeared to stabilize the MMP-1 mRNA, resulting in reduced turnover of the transcript. These data suggest that IFN-γ enhances MMP gene expression at the post-transcriptional level, The altered MMP expression by IFN-γ without concomitant effect on TIMP gene expression potentially leads to imbalance between these proteases and their inhibitors, and enhanced proteolytic activity may play a role in the remodeling of cutaneous tissue involving inflammatory processes, such as wound healing.