INTERLEUKIN-10 MODULATES TYPE-I COLLAGEN AND MATRIX METALLOPROTEASE GENE-EXPRESSION IN CULTURED HUMAN SKIN FIBROBLASTS
INTERLEUKIN-10 MODULATES TYPE-I COLLAGEN AND MATRIX METALLOPROTEASE GENE-EXPRESSION IN CULTURED HUMAN SKIN FIBROBLASTS
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DOI：
10.1172/jci117618
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发表时间：
1994-12-01
影响因子：
15.9
通讯作者：
UITTO, J
中科院分区：
文献类型：
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作者：
REITAMO, S;REMITZ, A;UITTO, J
IL-10最初分离自小鼠辅助性T细胞，是一种对多种白细胞介素具有调节功能的细胞因子。在这项研究中，我们表明，重组人IL-10的影响，参与细胞外基质的合成和重塑人真皮成纤维细胞培养物中的几个基因的表达。通过北方印迹分析判断，I型胶原基因表达被下调，而胶原酶和基质溶解素基因表达被IL-10显著增强。未观察到对金属蛋白酶组织抑制剂mRNA水平的影响。瞬时转染皮肤成纤维细胞与I型胶原启动子/氯霉素乙酰转移酶报告基因结构显示下调IL-10，这表明在转录水平上的抑制。与对照培养物相比，IL-10孵育导致人I型胶原抗体的成纤维细胞培养物的免疫染色减少。相反，用抗人胶原酶的抗体对IL-10处理的培养物进行免疫染色导致免疫染色增加。这项研究表明IL-10在细胞外基质的分解和重塑中的作用。
IL-10, originally isolated from mouse helper T cells, is a cytokine with regulatory functions on a number of interleukins. In this study we show that recombinant human IL-10 affects the expression of several genes involved in extracellular matrix synthesis and remodeling in human dermal fibroblast cultures. As judged by Northern blot analyses, type I collagen gene expression was downregulated, while collagenase and stromelysin gene expression were markedly enhanced by IL-10. No effect on tissue inhibitor of metalloproteases mRNA levels was noted. Transient transfections of skin fibroblasts with type I collagen promoter/chloramphenicol acetyl transferase reporter gene constructs showed downregulation by IL-10, suggesting inhibition at the transcriptional level. When compared with control cultures, incubation with IL-10 resulted in a decrease in immunostaining of fibroblast cultures with antibodies to human type I collagen. In contrast, immunostaining of such IL-10-treated cultures with antibodies to human collagenase resulted in an increase in immunostaining. This study suggests a role for IL-10 in the breakdown and remodeling of the extracellular matrix.