Role of serum amyloid A as an intermediate in the IL-1 and PMA-stimulated signaling pathways regulating expression of rabbit fibroblast collagenase
Role of serum amyloid A as an intermediate in the IL-1 and PMA-stimulated signaling pathways regulating expression of rabbit fibroblast collagenase
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DOI：
10.1006/excr.1997.3783
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发表时间：
1997-12-15
影响因子：
3.7
通讯作者：
Fini, ME
中科院分区：
文献类型：
--
作者：
Strissel, KJ;Girard, MT;Fini, ME
基质金属蛋白酶胶原酶只有在生物重建需要时才由常驻组织细胞表达。外源性炎症和促生长细胞因子的加入刺激了早期传代成纤维细胞中胶原酶的表达，此外，胶原酶表达的信号响应佛波酯(PMA)或在传代早期成纤维细胞培养中改变细胞形状的药物被细胞外路由到自分泌细胞因子中间体IL-1α。重要的是，当成纤维细胞从组织中新鲜分离出来时，不能胜任IL-1α基因的表达，因此不能产生胶原酶来响应形状变形剂。然而，它们确实通过IL-1非依赖的途径产生少量的胶原酶来响应PMA，这一途径尚未得到进一步的表征。在这篇文章中，我们研究了第二个自分泌，血清淀粉样蛋白A3(SAA3)，在IL-1依赖和非依赖胶原酶基因表达中的作用。我们证明SAA3是外源性或内源性IL-1有效刺激胶原酶表达所必需的。此外，虽然新鲜分离的成纤维细胞不能表达IL-1α，但它们可以表达SAA3，这种自分泌介质独立于IL-1α发挥作用，控制PMA刺激的胶原酶表达的低水平。这些结果为胶原酶调节新出现的范例提供了进一步的证据，该范例强调信号的细胞外路由的要求。他们还表明，SAA3可能独立于IL-1α用于控制体内的组织重塑。(C)1997年学术出版社。
The matrix metalloproteinase collagenase is expressed by resident tissue cells only when needed for biological remodeling. Exogenous addition of inflammatory and growth-promoting cytokines stimulates collagenase expression in early passage fibroblast cultures, In addition, the signal for collagenase expression in response to phorbol-12-myristate-13 acetate (PMA) or to agents which alter cell shape in early passage fibroblast cultures is routed extracellularly to an autocrine cytokine intermediate, IL-1 alpha. Importantly, fibroblasts, when freshly isolated from the tissue, are not competent for IL-1 alpha gene expression and, therefore, cannot produce collagenase in response to shape change agents. However, they do make a small amount of collagenase in response to PMA via an IL-1-independent pathway that has not been further characterized. In this paper, we investigate the role of a second autocrine, serum amyloid A3 (SAA3), in IL-1-dependent and -independent collagenase gene expression. We demonstrate that SAA3 is required for effective stimulation of collagenase expression by either exogenous or endogenous IL-1. Furthermore, while freshly isolated fibroblasts cannot express IL-1 alpha they can express SAA3, and this autocrine mediator acts independently of IL-1 alpha to control the low level of collagenase expression that can be stimulated by PMA. These results provide further evidence for a newly emerging paradigm of collagenase regulation which emphasizes the requirement for extracellular routing of signals. They also suggest that SAA3 might be utilized independently of IL-1 alpha to control tissue remodeling in vivo. (C) 1997 Academic Press.