Detection of receptors for lnterleukin-6, lnterleukin-11, leukemia inhibitory factor, oncostatin M, and ciliary neurotrophic factor in bone marrow stromal/ osteoblastic cells

Abstract

The functional receptor complexes assembled in response to interleukin-6 and -11 (IL-6 and IL-11), leukemia inhibitory factor (LIF), oncostatin M (OSM), and ciliary neurotrophic factor (CNTF), all involve the signal transducer gp130: IL-6 and IL-11 induce homodimerization of gp130, while the rest heterodimerize gp130 with other gp130-related β subunits. Some of these cytokines (IL-6, IL-11, and CNTF) also require a specificity-determining α subunit not directly involved in signaling. We have searched for functional receptor complexes for these cytokines in cells of the bone marrow stromal/osteoblastic lineage, using tyrosine phosphorylation of the β subunits as a detection assay. Collectively, murine calvaria cells, bone marrow-derived murine cell lines (+/+LDA11 and MBA13.2), as well as murine (MC3T3-E1) and human (MG-63) osteoblast-like cell lines displayed all the previously recognized α and β subunits of this family of receptors. However, individual cell types had different constellations of α and β subunits. In addition and in difference to the other cell types examined, MC3T3-E1 cells expressed a heretofore unrecognized form of gp130; and MG-63 displayed an alternative form (type II) of the OSM receptor. These findings establish that stromal/osteoblastic cells are targets for the actions of all the members of the cytokine subfamily that shares the gp130 signal transducer; and suggest that different receptor repertoires may be expressed at different stages of differentiation of this lineage.