INTERLEUKIN-1 IS AN AUTOCRINE REGULATOR OF HUMAN ENDOTHELIAL-CELL GROWTH
INTERLEUKIN-1 IS AN AUTOCRINE REGULATOR OF HUMAN ENDOTHELIAL-CELL GROWTH
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DOI：
10.1073/pnas.87.17.6487
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发表时间：
1990-09-01
影响因子：
11.1
通讯作者：
STERN, DM
中科院分区：
文献类型：
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作者：
COZZOLINO, F;TORCIA, M;STERN, DM
内皮细胞的增殖是通过生长因子的自分泌和同源表面受体的表达来调节的。在这项研究中，我们证明了白细胞介素1 （IL-1）是体外和体内内皮细胞生长的抑制剂。IL-1抑制生长，培养内皮细胞在G1期；增殖抑制是剂量依赖性的，并与内皮表面IL-1受体的占用并行发生。在血管生成模型中，IL-1可以抑制成纤维细胞生长因子诱导的血管形成。通过观察内源性IL-1占据细胞表面受体抑制细胞生长，证实了IL-1对内皮细胞增殖影响的自分泌性质。这一发现的潜在意义是通过在人脐静脉的天然内皮中检测IL-1来强调的。研究表明，IL-1可降低内皮细胞上高亲和力成纤维细胞生长因子结合位点的表达，提示IL-1抑制内皮细胞生长的机制。这些结果指出了IL-1在调节血管生长中的潜在重要作用，并提示自分泌抑制因子的产生可能是控制正常细胞增殖的一种机制。
Proliferation of endothelial cells is regulated through the autocrine production of growth factors and the expression of cognate surface receptors. In this study, we demonstrate that interleukin 1 (IL-1) is an inhibitor of endothelial growth in vitro and in vivo. IL-1 arrested growing, cultured endothelial cells in G1 phase; inhibition of proliferation was dose dependent and occurred in parallel with occupancy of endothelial surface IL-1 receptors. In an angiogenesis model, IL-1 could inhibit fibroblast growth factor-induced vessel formation. The autocrine nature of the IL-1 effect on endothelial proliferation was demonstrated by the observation that occupancy of cell-surface receptors by endogenous IL-1 depressed cell growth. The potential significance of this finding was emphasized by the detection of IL-1 in the native endothelium of human umbilical veins. A mechanism by which IL-1 may exert its inhibitory effect on endothelial cell growth was suggested by studies showing that IL-1 decreased the expression of high-affinity fibroblast growth factor binding sites on endothelium. These results point to a potentially important role of IL-1 in regulating blood vessel growth and suggest that autocrine production of inhibitory factors may be a mechanism controlling proliferation of normal cells.