Interleukin-6 and its soluble receptor cause a marked induction of collagenase 3 expression in rat osteoblast cultures
Interleukin-6 and its soluble receptor cause a marked induction of collagenase 3 expression in rat osteoblast cultures
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DOI：
10.1074/jbc.272.18.12144
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发表时间：
1997-05-02
影响因子：
4.8
通讯作者：
Canalis, E
中科院分区：
文献类型：
--
作者：
Franchimont, N;Rydziel, S;Canalis, E
白介素 6 (IL-6) 是一种由骨骼细胞产生的细胞因子，可增加骨吸收，但其对胶原酶表达的影响尚不清楚。我们测试了 IL-6 及其可溶性受体对胎鼠颅盖成骨细胞富集细胞（Ob 细胞）中胶原酶 3 表达的影响。 IL-6 导致胶原酶 mRNA 水平小幅增加，但在 IL-6 可溶性受体 (IL-6sR) 存在的情况下，2-24 小时后，IL-6 导致胶原酶转录物显着增加。此外，单独测试时，IL-6sR 会增加胶原酶 mRNA。 IL-6 和 IL-6sR 增加免疫反应性胶原酶水平。放线菌酮和吲哚美辛不能阻止 IL-6 和 IL-6sR 对胶原酶 mRNA 水平的影响。 IL-6和IL-6sR不会改变转录停滞的Ob细胞中胶原酶mRNA的衰减，并增加Ob细胞中胶原酶异质核RNA的水平和胶原酶基因转录率。 IL-6 和 IL-6sR 增加了 MC3T3 细胞中的胶原酶 3 mRNA，但在皮肤成纤维细胞中仅适度增加。 IL-6 和 IL-6sR 增强金属蛋白酶组织抑制剂 1 的表达。 总之，IL-6 在 IL-6sR 存在的情况下，通过转录机制增加成骨细胞中胶原酶 3 的合成。这种作用可能有助于 IL-6 对骨基质降解和骨吸收的作用。
Interleukin-6 (IL-6), a cytokine produced by skeletal cells, increases bone resorption, but its effects on collagenase expression are unknown. We tested the effects of IL-6 and its soluble receptor on collagenase 3 expression in osteoblast enriched cells from fetal rat calvariae (Ob cells). IL-6 caused a small increase in collagenase mRNA levels, but in the presence of IL-6-soluble receptor (IL-6sR), IL-6 caused a marked increase in collagenase transcripts after 2-24 h. In addition, IL-6sR increased collagenase mRNA when tested alone. IL-6 and IL-6sR increased immunoreactive collagenase levels. Cycloheximide and indomethacin did not prevent the effect of IL-6 and IL-6sR on collagenase mRNA levels. IL-6 and IL-6sR did not alter the decay of collagenase mRNA in transcriptionally arrested Ob cells and increased the levels of collagenase heterogeneous nuclear RNA and the rate of collagenase gene transcription in Ob cells. IL-6 and IL-6sR increased collagenase 3 mRNA in MC3T3 cells but only modestly in skin fibroblasts. IL-6 and IL-6sR enhanced the expression of tissue inhibitor of metalloproteinases 1. In conclusion, IL-6, in the presence of IL-6sR, increases collagenase 3 synthesis in osteoblasts by transcriptional mechanisms. This effect may contribute to the action of IL-6 on bone matrix degradation and bone resorption.