Franchimont N, Rydziel S, Delany A M, Canalis E
Department of Research, Saint Francis Hospital and Medical Center, Hartford, Connecticut 06105, USA.
J Biol Chem. 1997 May 2;272(18):12144-50. doi: 10.1074/jbc.272.18.12144.
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.
白细胞介素-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及其可溶性受体对来自胎鼠颅骨的富含成骨细胞的细胞（成骨细胞）中胶原酶3表达的影响。IL-6使胶原酶mRNA水平略有增加，但在存在IL-6可溶性受体（IL-6sR）的情况下，IL-6在2-24小时后使胶原酶转录物显著增加。此外，单独测试时IL-6sR可增加胶原酶mRNA。IL-6和IL-6sR增加了免疫反应性胶原酶水平。放线菌酮和消炎痛不能阻止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成骨细胞中胶原酶mRNA的衰变，并增加了成骨细胞中胶原酶不均一核RNA的水平和胶原酶基因的转录速率。IL-6和IL-6sR在MC3T3细胞中增加了胶原酶3 mRNA，但在皮肤成纤维细胞中仅略有增加。IL-6和IL-6sR增强了金属蛋白酶组织抑制剂1的表达。总之，在存在IL-6sR的情况下，IL-6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。
