Oncostatin M is produced by monocytes and T cells after cell activation, adherent macrophages, and various T cell lines. Oncostatin M is a member of the IL-6-related cytokine subfamily that includes IL-6, IL-11, LIF, CNTF and CT-1. Oncostatin M mediates its bioactivities through two different heterodimer receptors. They both involve gp130 as a signal transducing moiety, which is found also in receptors for a number of other cytokines. When gp130 dimerizes with LIF receptor beta subunit this generates the high affinity type 1 OSM receptor. When gp130 dimerizes with a protein known as OSM receptor beta this generates the type 2 OSM receptor. Both OSM receptors activate the receptor-associated Janus kinases JAK1, JAK2, and TYK2. Signaling also involves the transcriptional activators STAT3 and STAT5b (see also: STAT proteins) were specifically activated through the gp130-OSM-R-beta type II heterocomplex. The signaling pathway differences observed between the common type I LIF/OSM receptor and the specific type II OSM receptor might explain some of the bioactivities specifically displayed by OSM. Oncostatin M inhibits the growth of several tumor cell lines (A375 melanoma, lung carcinomas). The antiproliferative activity of oncostatin M for some cell lines is synergised by TGF-beta and IFN-gamma. It promotes the growth of human fibroblasts, vascular smooth muscle cells, and some normal cell lines. Oncostatin can inhibit the proliferation of murine M1 myeloid leukemic cells and induces their differentiation into macrophage-like cells, a function shared by LIF, G- CSF, and IL-6.

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