27. – Oncostatin M

Publisher Summary This chapter focuses on oncostatin M (OM). Human OM (hOM) is a single-chain polypeptide that was originally identified for its growth-inhibitory effects on human tumor cell lines and contrary growth stimulatory effects on several normal fibroblast lines. The hOM was isolated from media conditioned by phorbol 12-myristate 13-acetate (PMA)-treated human histiocytic lymphoma cells and from phytohemagglutinin (PHA)-activated human T lymphocytes. The hOM is structurally and functionally related to a family of hematopoietic and neurotropic cytokines whose members include leukemia inhibitory factor (LIF), interleukin-6 (IL-6), granulocyte colony-stimulating factor (G-CSF), ciliary neurotropic factor (CNTF), myelomonocytic growth factor (MGF), interleukin-II (IL-II), and cardiotrophin. The human, simian, and bovine genes for OM are approximately 5 kb in length. The human gene consists of three exons and two introns, and the exon/intron boundary sequences conform to the AT-GT rule for nucleotides flanking the eukaryotic exon boundaries. The hOM contains five cysteine residues, four of which form intramolecular disulfide bonds. Very few cell types have been shown to synthesize and secrete the hOM. U-937 histiocytic lymphoma cells do not constitutively express the hOM, but upon treatment with PMA these cells acquire many of the characteristics of macrophages and produce the hOM. Human macrophages, following stimulation with endotoxin, also secrete the hOM. The hOM acts on various cell types and elicits various diverse responses. The nature and magnitude of these responses are likely to be modulated by the cellular environment and the presence of other cytokines in vivo.