PERSISTENCE OF A REDUCED-COLLAGEN-PRODUCING PHENOTYPE IN CULTURED SCLERODERMA FIBROBLASTS AFTER SHORT-TERM EXPOSURE TO INTERFERONS
PERSISTENCE OF A REDUCED-COLLAGEN-PRODUCING PHENOTYPE IN CULTURED SCLERODERMA FIBROBLASTS AFTER SHORT-TERM EXPOSURE TO INTERFERONS
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DOI：
10.1172/jci112956
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发表时间：
1987-05-01
影响因子：
15.9
通讯作者：
BERMAN, B
中科院分区：
文献类型：
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作者：
DUNCAN, MR;BERMAN, B
短暂暴露于炎症相关的成纤维细胞刺激因子似乎通过诱导来自硬皮病皮肤和其他纤维化组织的成纤维细胞培养物所显示的持续激活的表型来启动纤维化。为了确定一类成纤维细胞抑制因子干扰素（IFN）是否通过作为持续的成纤维细胞失活剂在终止纤维化中发挥作用，我们通过短期暴露于IFN- α，抑制（40-60%）正常真皮成纤维细胞和高胶原生成硬皮病成纤维细胞的生长和胶原生成。度量。，或者。伽马…在随后的传代培养中，在缺乏ifn的情况下，正常成纤维细胞的生长和胶原蛋白的产生以及硬皮病成纤维细胞的生长在两到三次传代后增加到未处理的对照水平。相比之下，硬皮病成纤维细胞的胶原生成至少被抑制了5次（18次细胞加倍），并且在随后的IFN暴露中没有进一步抑制。这些数据表明ifn可能通过抑制持续激活的成纤维细胞功能来帮助终止纤维化。
Transient exposure to inflammation-associated, fibroblast-stimulatory factors appears to initiate fibrosis by inducing the persistently activated phenotypes displayed by fibroblast cultures derived from scleroderma skin and other fibrotic tissues. To determine whether one class of fibroblast-inhibitory factors, the interferons (IFNs), plays a role in terminating fibrosis by acting as persistent fibroblast deactivators, we inhibited (40-60%) the growth and collagen production of normal dermal fibroblasts and hypercollagen-producing scleroderma fibroblasts by short-term exposure to IFN-.alpha., .beta., or .gamma.. During subsequent subculture in the absence of IFNs, the growth and collagen production of normal fibroblasts and the growth of scleroderma fibroblasts increased to untreated control levels after two to three passages. In contrast, collagen production by scleroderma fibroblasts remained inhibited for at least five passages (18 cell doublings) and was not further suppressed by subsequent IFN exposure. These data suggest that IFNs may help terminate fibrosis by suppressing persistently activated fibroblast functions.