Barillé S, Collette M, Thabard W, Bleunven C, Bataille R, Amiot M
INSERM U463, Institut de biologie, 9 quai Moncousu 44093, Nantes cedex 01, France.
Cytokine. 2000 Sep;12(9):1426-9. doi: 10.1006/cyto.2000.0734.
IL-6 mediates its activity through a cell surface receptor composed of a signal transducing protein, CD130, and a ligand-binding protein which exists in membrane-bound form (CD126) or in soluble form (sIL-6R alpha). Interestingly, sIL-6R alpha combined with IL-6 is able to interact with CD130 leading to the intracellular cascade of activation. In the present study, using flow cytometry, we show that stromal cells from human bone marrow (BMSC) express CD130 but not CD126. We demonstrate that BMSC are responsive to IL-6 only in the presence of exogenous sIL-6R alpha. Indeed, exogenous sIL-6R alpha induces in BMSC the production of its own ligand, IL-6, and of both MMP-1 and MMP-2, two matrix metalloproteinases involved in bone resorption and in tumour spreading, respectively. Since myeloma cells release sIL-6R alpha in the close vicinity of BMSC, these data suggest a role for this factor in the pathophysiology of multiple myeloma, a B-cell malignancy dependent on IL-6 for its growth and characterized by bone destruction.
白细胞介素-6（IL-6）通过一种细胞表面受体介导其活性，该受体由信号转导蛋白CD130和配体结合蛋白组成，配体结合蛋白以膜结合形式（CD126）或可溶性形式（sIL-6Rα）存在。有趣的是，sIL-6Rα与IL-6结合后能够与CD130相互作用，从而引发细胞内的激活级联反应。在本研究中，我们使用流式细胞术表明，人骨髓基质细胞（BMSC）表达CD130，但不表达CD126。我们证明，只有在外源sIL-6Rα存在的情况下，BMSC才对IL-6有反应。事实上，外源性sIL-6Rα可诱导BMSC产生其自身的配体IL-6以及基质金属蛋白酶-1（MMP-1）和基质金属蛋白酶-2（MMP-2），这两种基质金属蛋白酶分别参与骨吸收和肿瘤扩散。由于骨髓瘤细胞在BMSC附近释放sIL-6Rα，这些数据表明该因子在多发性骨髓瘤的病理生理学中发挥作用，多发性骨髓瘤是一种依赖IL-6生长且以骨破坏为特征的B细胞恶性肿瘤。
