Soluble IL-6R alpha upregulates IL-6, MMP-1 and MMP-2 secretion in bone marrow stromal cells

IL-6 mediates its activity through a cell surface receptor composed of a si gnal transducing protein, CD130, and a ligand-binding protein which exists in membrane-bound form (CD126) or in soluble form (sIL-6R alpha). Interesti ngly, sIL-6Ra combined with IL-6 is able to interact with CD130 leading to the intracellular cascade of activation. In the present study, using flow c ytometry, 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 i n the presence of exogenous sIL-6R alpha. Indeed, exogenous sIL-6R alpha in duces 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 tu mour spreading, respectively. Since myeloma cells release sIL-6R alpha in t he 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. (C) 2000 Academic Pr ess.