Cloning and biological activity of murine oncostatin M.

Oncostatin M (OSM) is a member of the interleukin-6/leukemia inhibitory factor (LIF) family cytokines. While human OSM (hOSM) has been characterized, the murine counterpart had not been isolated. We cloned a murine OSM (mOSM) cDNA as a gene that is induced in hematopoietic cells by a subset of cytokines including IL-3, GM-CSF and Epo. Identity of mOSM was based on overall homology to hOSM and chromosomal gene localization. Human OSM is known to exhibit biological activities similar to LIF, because they share the same functional receptor composed of the LIF receptor and gp130. As compared to hOSM, however, a 1000-fold higher concentrations of mOSM was required to stimulate proliferation of LIF-dependent murine DA1a cells, differentiation of M1 macrophage cells, and inhibition of ES cell differentiation. On the other hand, mOSM inhibited growth of NIH3T3 cells at a 1000-fold lower concentration than that of hOSM. These results indicate that mOSM functions through a receptor which is distinct from that of the LIF receptor. Studies on the physiological role of OSM is underway.