Oncostatin M is a neuroprotective cytokine that inhibits excitotoxic injury in vitro and in vivo

2006 ◽  
Vol 20 (13) ◽  
pp. 2369-2371 ◽  
Author(s):  
Thomas W. Weiss ◽  
Andre L. Samson ◽  
Be'eri Niego ◽  
Philip B. Daniel ◽  
Robert L. Medcalf ◽  
...  
Keyword(s):  
Oncostatin M ◽  
Excitotoxic Injury

scholarly journals A Dual Role for Oncostatin M Signaling in the Differentiation and Death of Mammary Epithelial Cells in Vivo

2008 ◽  
Vol 22 (12) ◽  
pp. 2677-2688 ◽  
Author(s):  
Paul G. Tiffen ◽  
Nader Omidvar ◽  
Nuria Marquez-Almuina ◽  
Dawn Croston ◽  
Christine J. Watson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
Mammary Epithelial Cells ◽  
Mammary Epithelial ◽  
Oncostatin M ◽  
Specific Gene ◽  
Mammary Involution

Abstract Recent studies in breast cancer cell lines have shown that oncostatin M (OSM) not only inhibits proliferation but also promotes cell detachment and enhances cell motility. In this study, we have looked at the role of OSM signaling in nontransformed mouse mammary epithelial cells in vitro using the KIM-2 mammary epithelial cell line and in vivo using OSM receptor (OSMR)-deficient mice. OSM and its receptor were up-regulated approximately 2 d after the onset of postlactational mammary regression, in response to leukemia inhibitory factor (LIF)-induced signal transducer and activator of transcription-3 (STAT3). This resulted in sustained STAT3 activity, increased epithelial apoptosis, and enhanced clearance of epithelial structures during the remodeling phase of mammary involution. Concurrently, OSM signaling precipitated the dephosphorylation of STAT5 and repressed expression of the milk protein genes β-casein and whey acidic protein (WAP). Similarly, during pregnancy, OSM signaling suppressed β-casein and WAP gene expression. In vitro, OSM but not LIF persistently down-regulated phosphorylated (p)-STAT5, even in the continued presence of prolactin. OSM also promoted the expression of metalloproteinases MMP3, MMP12, and MMP14, which, in vitro, were responsible for OSM-specific apoptosis. Thus, the sequential activation of IL-6-related cytokines during mammary involution culminates in an OSM-dependent repression of epithelial-specific gene expression and the potentiation of epithelial cell extinction mediated, at least in part, by the reciprocal regulation of p-STAT5 and p-STAT3.

scholarly journals Oncostatin M Induces Angiogenesis In Vitro and In Vivo

1999 ◽  
Vol 19 (8) ◽  
pp. 1835-1842 ◽  
Author(s):  
Marc Vasse ◽  
Jérôme Pourtau ◽  
Véronique Trochon ◽  
Marc Muraine ◽  
Jean-Pierre Vannier ◽  
...  
Keyword(s):  
Oncostatin M

scholarly journals Thrombocytopoietic properties of oncostatin M

Blood ◽  
1995 ◽  
Vol 86 (4) ◽  
pp. 1310-1315 ◽  
Author(s):  
PM Wallace ◽  
JF MacMaster ◽  
JR Rillema ◽  
J Peng ◽  
SA Burstein ◽  
...  
Keyword(s):  
Colony Formation ◽  
Oncostatin M ◽  
Platelet Recovery ◽  
Cell Counts ◽  
Animal Data ◽  
Maturation Factor ◽  
Biologic Effects ◽  
Potential Clinical Utility

Oncostatin M (OM) is a 28-kD glycoprotein that exhibits a panoply of biologic effects. Based on histologic observations of increased splenic megakaryocytes in nude mice implanted with an OM-secreting cell line, the thrombocytopoietic properties of OM in mice were investigated in culture and in vivo. Alone, OM did not induce megakaryocytic colony formation, but in combination with murine interleukin-3 (IL-3), OM markedly enhanced colony formation. The effects of OM on colony formation were similar to those of IL-6. OM alone augmented acetylcholinesterase in short-term marrow cultures. In normal mice, the administration of OM augmented platelet counts without increasing other circulating blood cell counts. The increment in counts exceeded that observed with IL-6. The kinetics of the OM response suggested that maximal increases in platelets occurred 3 days after the cessation of OM administration, irrespective of the duration of administration. In irradiated mice, OM administration accelerated platelet recovery and prevented the decrease in red blood cells observed in irradiated control animals. The data show that OM behaves as a megakaryocytic maturation factor in vitro and augments platelet production in vivo. Based on these animal data, OM may have potential clinical utility as a thrombocytopoietic agent.

scholarly journals Loss of Oncostatin M Signaling in Adipocytes Induces Insulin Resistance and Adipose Tissue Inflammation in Vivo

2016 ◽  
Vol 291 (33) ◽  
pp. 17066-17076 ◽  
Author(s):  
Carrie M. Elks ◽  
Peng Zhao ◽  
Ryan W. Grant ◽  
Hardy Hang ◽  
Jennifer L. Bailey ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Cell Types ◽  
Oncostatin M ◽  
Adipose Tissue Inflammation ◽  
High Fat ◽  
Tissue Inflammation ◽  
Fat Feeding

Oncostatin M (OSM) is a multifunctional gp130 cytokine. Although OSM is produced in adipose tissue, it is not produced by adipocytes. OSM expression is significantly induced in adipose tissue from obese mice and humans. The OSM-specific receptor, OSM receptor β (OSMR), is expressed in adipocytes, but its function remains largely unknown. To better understand the effects of OSM in adipose tissue, we knocked down Osmr expression in adipocytes in vitro using siRNA. In vivo, we generated a mouse line lacking Osmr in adiponectin-expressing cells (OSMRFKO mice). The effects of OSM on gene expression were also assessed in vitro and in vivo. OSM exerts proinflammatory effects on cultured adipocytes that are partially rescued by Osmr knockdown. Osm expression is significantly increased in adipose tissue T cells of high fat-fed mice. In addition, adipocyte Osmr expression is increased following high fat feeding. OSMRFKO mice exhibit increased insulin resistance and adipose tissue inflammation and have increased lean mass, femoral length, and bone volume. Also, OSMRFKO mice exhibit increased expression of Osm, the T cell markers Cd4 and Cd8, and the macrophage markers F4/80 and Cd11c. Interestingly, the same proinflammatory genes induced by OSM in adipocytes are induced in the adipose tissue of the OSMRFKO mouse, suggesting that increased expression of proinflammatory genes in adipose tissue arises both from adipocytes and other cell types. These findings suggest that adipocyte OSMR signaling is involved in the regulation of adipose tissue homeostasis and that, in obesity, OSMR ablation may exacerbate insulin resistance by promoting adipose tissue inflammation.

scholarly journals Oncostatin M-induced astrocytic tissue inhibitor of metalloproteinases-1 drives remyelination

2020 ◽  
Vol 117 (9) ◽  
pp. 5028-5038 ◽  
Author(s):  
Evelien Houben ◽  
Kris Janssens ◽  
Doryssa Hermans ◽  
Jennifer Vandooren ◽  
Chris Van den Haute ◽  
...  
Keyword(s):  
Therapeutic Potential ◽  
Treatment Options ◽  
Oncostatin M ◽  
Tissue Inhibitor Of Metalloproteinases ◽  
Tissue Inhibitor ◽  
Human Value ◽  
Demyelinating Disorders ◽  
Downstream Mediator

The brain’s endogenous capacity to restore damaged myelin deteriorates during the course of demyelinating disorders. Currently, no treatment options are available to establish remyelination. Chronic demyelination leads to damaged axons and irreversible destruction of the central nervous system (CNS). We identified two promising therapeutic candidates which enhance remyelination: oncostatin M (OSM), a member of the interleukin-6 family, and downstream mediator tissue inhibitor of metalloproteinases-1 (TIMP-1). While remyelination was completely abrogated in OSMRβ knockout (KO) mice, OSM overexpression in the chronically demyelinated CNS established remyelination. Astrocytic TIMP-1 was demonstrated to play a pivotal role in OSM-mediated remyelination. Astrocyte-derived TIMP-1 drove differentiation of oligodendrocyte precursor cells into mature oligodendrocytes in vitro. In vivo, TIMP-1 deficiency completely abolished spontaneous remyelination, phenocopying OSMRβ KO mice. Finally, TIMP-1 was expressed by human astrocytes in demyelinated multiple sclerosis lesions, confirming the human value of our findings. Taken together, OSM and its downstream mediator TIMP-1 have the therapeutic potential to boost remyelination in demyelinating disorders.

scholarly journals The Enigmatic Cytokine Oncostatin M and Roles in Disease

2013 ◽  
Vol 2013 ◽  
pp. 1-23 ◽  
Author(s):  
Carl D. Richards
Keyword(s):  
Rheumatoid Arthritis ◽  
Cardiovascular Disease ◽  
Cell Proliferation ◽  
Chronic Inflammation ◽  
Inflammatory Disease ◽  
Oncostatin M ◽  
Therapeutic Approaches ◽  
Pleiotropic Functions

Oncostatin M is a secreted cytokine involved in homeostasis and in diseases involving chronic inflammation. It is a member of the gp130 family of cytokines that have pleiotropic functions in differentiation, cell proliferation, and hematopoetic, immunologic, and inflammatory networks. However, Oncostatin M also has activities novel to mediators of this cytokine family and others and may have fundamental roles in mechanisms of inflammation in pathology. Studies have explored Oncostatin M functions in cancer, bone metabolism, liver regeneration, and conditions with chronic inflammation including rheumatoid arthritis, lung and skin inflammatory disease, atherosclerosis, and cardiovascular disease. This paper will review Oncostatin M biology in a historical fashion and focus on its unique activities, in vitro and in vivo, that differentiate it from other cytokines and inspire further study or consideration in therapeutic approaches.

scholarly journals Murine Oncostatin M Stimulates Mouse Synovial Fibroblasts in Vitro and Induces Inflammation and Destruction in Mouse Joints in Vivo

2000 ◽  
Vol 157 (4) ◽  
pp. 1187-1196 ◽  
Author(s):  
Carrie Langdon ◽  
Christine Kerr ◽  
Mohammed Hassen ◽  
Takahiko Hara ◽  
A. Larry Arsenault ◽  
...  
Keyword(s):  
Synovial Fibroblasts ◽  
Oncostatin M

scholarly journals Oncostatin M suppresses oestrogen receptor-α expression and is associated with poor outcome in human breast cancer

2012 ◽  
Vol 19 (2) ◽  
pp. 181-195 ◽  
Author(s):  
Nathan R West ◽  
Leigh C Murphy ◽  
Peter H Watson
Keyword(s):  
Breast Cancer ◽  
Mrna Expression ◽  
Oestrogen Receptor ◽  
Oncostatin M ◽  
Breast Cancer Cell Lines ◽  
Dependent Manner ◽  
Cancer Management ◽  
Er Expression

The most important clinical biomarker for breast cancer management is oestrogen receptor alpha (ERα). Tumours that express ER are candidates for endocrine therapy and are biologically less aggressive, while ER-negative tumours are largely treated with conventional chemotherapy and have a poor prognosis. Despite its significance, the mechanisms regulating ER expression are poorly understood. We hypothesised that the inflammatory cytokine oncostatin M (OSM) can downregulate ER expression in breast cancer. Recombinant OSM potently suppressed ER protein and mRNA expression in vitro in a dose- and time-dependent manner in two human ER+ breast cancer cell lines, MCF7 and T47D. This was dependent on the expression of OSM receptor beta (OSMRβ) and could be blocked by inhibition of the MEKK1/2 mitogen-activated protein kinases. ER loss was also necessary for maximal OSM-induced signal transduction and migratory activity. In vivo, high expression of OSM and OSMR mRNA (determined by RT-PCR) was associated with reduced ER (P<0.01) and progesterone receptor (P<0.05) protein levels in a cohort of 70 invasive breast cancers. High OSM and OSMR mRNA expression was also associated with low expression of ESR1 (ER, P<0.0001) and ER-regulated genes in a previously published breast cancer gene expression dataset (n=321 cases). In the latter cohort, high OSMR expression was associated with shorter recurrence-free and overall survival in univariate (P<0.0001) and multivariate (P=0.022) analyses. OSM signalling may be a novel factor causing suppression of ER and disease progression in breast cancer.

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