Oncostatin M is a member of a cytokine family that includes leukemia-inhibitory factor, granulocyte colony-stimulating factor, and interleukin 6.
نویسندگان
چکیده
Oncostatin M (OSM), a glycoprotein of Mr approximately 28,000 produced by activated monocyte and T-lymphocyte cell lines, was previously identified by its ability to inhibit the growth of cells from melanoma and other solid tumors. We have detected significant similarities in the primary amino acid sequences and predicted secondary structures of OSM, leukemia-inhibitory factor (LIF), granulocyte colony-stimulating factor (G-CSF), and interleukin 6 (IL-6). Analysis of the genes encoding these proteins revealed a shared exon organization, suggesting evolutionary descent from a common ancestral gene. Using a panel of DNAs from somatic cell hybrids, we have shown that OSM, like LIF, is located on human chromosome 22. We have also demonstrated that OSM has the ability to inhibit the proliferation of murine M1 myeloid leukemic cells and can induce their differentiation into macrophage-like cells, a function shared by LIF, G-CSF, and IL-6. We propose that OSM, LIF, G-CSF, and IL-6 are structurally related members of a cytokine family that have in common the ability to modulate differentiation of a variety of cell types.
منابع مشابه
Homology model for oncostatin M based on NMR structural data.
Oncostatin M (OM) is a member of the cytokine family which regulates the proliferation and differentiation of a variety of cell types and includes interleukin-6 (IL-6), leukemia inhibitory factor (LIF), and granulocyte-colony stimulating factor (G-CSF). This family of proteins adopts a four-helix bundle fold with up-up-down-down topology and contains intramolecular disulfide bonds. Since an X-r...
متن کاملRegulation of granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor expression by oncostatin M.
Oncostatin M (OM) is structurally and functionally related to a subclass of hematopoietic cytokines including leukemia-inhibitory factor (LIF), ciliary neurotrophic factor (CNTF), granulocyte colony-stimulating factor (G-CSF), and interleukin-6 (IL-6). Using human endothelial cells (HEC) as a model for cytokine regulation of hematopoietic growth factor expression, we tested OM as an inducer of ...
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The effects of oncostatin M on the expression of different cytochrome P450 (CYP) isozymes has been investigated in human hepatocytes. The dose-response and time-course analyses of effects on CYP1A2 and CYP3A4 isozymes revealed that maximal inhibition was reached after 48 hr of exposure of human hepatocytes to 25 units/ml oncostatin M. Reductions in CYP1A2 and CYP3A4 activity produced by oncosta...
متن کاملDifferential regulation of macrophage differentiation in response to leukemia inhibitory factor/oncostatin-M/interleukin-6: the effect of enforced expression of the SCL transcription factor.
The physiologic program of macrophage differentiation normally proceeds in a coordinated manner in response to several different growth factors. Although the utilization of common receptor subunits may explain in part overlapping biologic functions, mechanisms by which unique actions are mediated remain obscure. We examined growth factor-induced macrophage differentiation in M1 leukemia cells t...
متن کاملOncostatin M decreases interleukin-1 β secretion by human synovial fibroblasts and attenuates an acute inflammatory reaction in vivo
Oncostatin M (OSM) is a pleiotropic cytokine of the IL-6 family and displays both pro-inflammatory and anti-inflammatory activities. We studied the impact of OSM on the gene activation profile of human synovial cells, which play a central role in the progression of inflammatory responses in joints. In synovial cells stimulated with lipopolysaccharide and recombinant human granulocyte-macrophage...
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ورودعنوان ژورنال:
- Proceedings of the National Academy of Sciences of the United States of America
دوره 88 19 شماره
صفحات -
تاریخ انتشار 1991