Soluble IL-6R alpha upregulated 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 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.
Barillé
S
S
INSERM U463, Institut de biologie, 9 quai Moncousu 44093, Nantes cedex 01, France. sbarille@nantes.inserm.fr
Collette
M
M
Thabard
W
W
Bleunven
C
C
Bataille
R
R
Amiot
M
M
D015703:Antigens, CD / Q000096:biosynthesis; D001853:Bone Marrow / Q000378:metabolism*; D001854:Bone Marrow Cells / Q000378:metabolism*; D002478:Cells, Cultured; D050822:Cytokine Receptor gp130; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism* / Q000494:pharmacology; D008024:Ligands; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D009101:Multiple Myeloma / Q000378:metabolism; D019947:Receptors, Interleukin-6 / Q000096:biosynthesis*; D015398:Signal Transduction; D017154:Stromal Cells / Q000378:metabolism*; D015854:Up-Regulation
D015703:Antigens, CD; C494199:IL6ST protein, human; D015850:Interleukin-6; D008024:Ligands; D008562:Membrane Glycoproteins; D019947:Receptors, Interleukin-6; D050822:Cytokine Receptor gp130; D020778:Matrix Metalloproteinase 2; D020781:Matrix Metalloproteinase 1