Lacey D L, Grosso L E, Moser S A, Erdmann J, Tan H L, Pacifici R, Villareal D T
Department of Pathology, Jewish Hospital of St. Louis, Washington University, Missouri 63110.
J Clin Invest. 1993 Apr;91(4):1731-42. doi: 10.1172/JCI116383.
IL-1-induced osteoblast IL-6 production represents one possible mechanism by which IL-1 augments bone resorption. In this report, we show that the murine osteoblastic cell line (MC3T3-E1) expresses type 1 IL-1 receptors based on 125I-HrIL1 alpha binding, blocked by type 1 IL-1R antibodies (35F5), and analysis of MC3T3 RNA by reverse transcription (RT)-DNA amplification and Northern analysis. MC3T3 cells do not express detectable type 2 IL-1R mRNA by RT-DNA amplification. IL-1 induces (IL-1 ED50, 0.1 pM) IL-6 production through the type 1 IL-1R as 35F5 antibodies block IL-1-stimulated IL-6 production. Vitamin D3 increases IL-1R expression dose- and metabolite-dependently, with 1,25-(OH)2D3 having the greatest potency, and also enhances IL-1's capacity to stimulate IL-6 production at low IL-1 levels. Both IL-1 and 1,25-(OH)2D3 induce type 1 IL-1R and not type 2 IL-1R upregulation based on ligand binding and RT-DNA amplification. Increased IL-1R expression requires a 5-7-h treatment and is protein/RNA synthesis dependent. These observations imply that IL-1-induced IL-6 production in osteoblasts is mediated by type 1 IL-1Rs and that increased IL-1R expression could play a role in mediating IL-1-induced skeletal responses.
白细胞介素-1（IL-1）诱导成骨细胞产生白细胞介素-6（IL-6）是IL-1增强骨吸收的一种可能机制。在本报告中，我们发现，基于125I-HrIL1α结合、被1型IL-1受体抗体（35F5）阻断以及通过逆转录（RT）-DNA扩增和Northern分析对MC3T3 RNA进行分析，小鼠成骨细胞系（MC3T3-E1）表达1型IL-1受体。通过RT-DNA扩增，MC3T3细胞未表达可检测到的2型IL-1R mRNA。IL-1通过1型IL-1受体诱导（IL-1半数有效剂量，0.1 pM）IL-6产生，因为35F5抗体可阻断IL-1刺激的IL-6产生。维生素D3以剂量和代谢物依赖的方式增加IL-1R表达，其中1,25-（OH）2D3的效力最大，并且在低IL-1水平时还增强IL-1刺激IL-6产生的能力。基于配体结合和RT-DNA扩增，IL-1和1,25-（OH）2D3均诱导1型IL-1R上调而不是2型IL-1R上调。IL-1R表达增加需要5至7小时的处理，并且依赖于蛋白质/RNA合成。这些观察结果表明，成骨细胞中IL-1诱导的IL-6产生是由1型IL-1受体介导的，并且IL-1R表达增加可能在介导IL-1诱导的骨骼反应中起作用。
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