Activation of macrophage promatrix metalloproteinase-9 by lipopolysaccharide-associated proteinases
Activation of macrophage promatrix metalloproteinase-9 by lipopolysaccharide-associated proteinases
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DOI：
10.4049/jimmunol.168.5.2449
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发表时间：
2002-03-01
影响因子：
4.4
通讯作者：
Lyons, JG
中科院分区：
文献类型：
--
作者：
Min, DQ;Moore, AG;Lyons, JG
LPS诱导单核细胞/巨噬细胞谱系细胞中前基质金属蛋白酶-9（proMMP 9）基因表达的上调。我们在这里证明，LPS制剂也能够激活proMMP 9由人类巨噬细胞或THP-1细胞通过LPS相关的蛋白酶，切割的N-末端前肽在一个或多个网站接近一个切割后与有机汞化合物激活。LPS相关蛋白酶是丝氨酸蛋白酶，其能够切割变性胶原（明胶）和哺乳动物丝氨酸蛋白酶抑制剂α（1）蛋白酶抑制剂，从而将细胞外基质周转的平衡进一步推向降解。在proMMP 9活化过程中，产生一种低分子量、失去亲和力的MMP 9抑制剂，可能来源于前肽。然而，LPS相关蛋白酶的抑制对proMMP 9的合成没有影响，表明它们的蛋白水解活性对于proMMP 9基因的上调信号传导不是必需的。
LPS induces an up-regulation of promatrix metalloproteinase-9 (proMMP9) gene expression in cells of the monocyte/macrophage lineage. We demonstrate here that LPS preparations are also able to activate proMMP9 made by human macrophages or THP-1 cells via LPS-associated proteinases, which cleave the N-terminal propeptide at a site or sites close to the one cleaved upon activation with organomercurial compounds. LPS-associated proteinases are serine proteinases that are able to cleave denatured collagens (gelatin) and the mammalian serine proteinase inhibitor, alpha(1) proteinase inhibitor, thereby pushing the balance of extracellular matrix turnover even further toward degradation. A low molecular mass, lose affinity inhibitor of MMP9, possibly derived from the propeptide, is generated during proMMP9 activation. However, inhibition of the LPS-associated proteinases had no effect on proMMP9 synthesis, indicating that their proteolytic activity seas not required for signaling the up-regulation of the proMMP9 gene.