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The Role of Oncostatin M in The Acute Phase Response
Published in Andrzej Mackiewicz, Irving Kushner, Heinz Baumann, Acute Phase Proteins, 2020
Carl D. Richards, Mohammed Shoyab
Oncostatin M was originally identified and characterized as a growth regulator for certain tumor and nontumor-derived cell lines. Oncostatin M (OM) is expressed in activated human T-lymphocytes8 and monocytes,9 and is secreted as a Mr 28,000 single-chain polypeptide with a unique primary structure10 and specific cell-surface receptors.11 OM inhibits the growth of human malignant melanoma and carcinoma cell lines12 as well as cultured bovine aortic endothelial cells,13 but stimulates the growth of certain cultured fibroblasts.10,12 Other bioactivities include stimulation of plasminogen activator activity in cultured bovine aortic endothelial cells,13 upregulation of expression of low density lipoprotein receptors in cultured human hepatoma cells,14 and induction of IL-6 expression in cultured human endothelial cells.15 In addition, OM has been implicated as a growth factor for Kaposi’s sarcoma cells.16,17
Immune Reconstitution after Hematopoietic Stem Cell Transplantation
Published in Richard K. Burt, Alberto M. Marmont, Stem Cell Therapy for Autoimmune Disease, 2019
Andreas Thiel, Tobias Alexander, Christian A. Schmidt, Falk Hiepe, Renate Arnold, Andreas Radbruch, Larissa Verda, Richard K. Burt
The necessity of a thymus for development of T cells from hematopoietic stem cells (HSC) has been questioned by the finding that CD3+ T cells may be generated ex vivo from CD34+ HSC in the absence of a thymus or thymic derived factors.39 Culturing highly purified CD34+ human HSC with flt-3 ligand, stem cell factor (SCF) and interleukin-2 (IL-2) may cause differentiation into CD3+CD4+ T cells that proliferate to mitogens and have a polyclonal TCR repertoire.40 It has also been demonstrated in mice that under non-physiologic cytokine stimulation, lymph nodes may generate functional TCRαβ T cells. Oncostatin M is an interleukin-6 like cytokine normally produced by hematopoietic cells. When transgenic mice express oncostatin M under a lymphocyte specific kinase (lck) promoter (p56lck), extrathymic T cell development occurs in mesenteric lymph nodes.41-44 Administration of oncostatin M protein in non-transgenic mice also produces a similar result.42-43 Whether any human T cells may be generated in vivo but outside of a thymus under normal or cytokine (oncostatin M or IL-7)45 stimulated conditions and what phenotype, number and functional characteristics these cells will have remains controversial. However, currently, a fully functional and polyclonal TCR repertoire requires a thymus and thymic function declines with age.
Regulation of Cell Functions
Published in Enrique Pimentel, Handbook of Growth Factors, 2017
Supernatants from activated human T lymphocytes are inhibitory for the growth of A375 human melanoma cells.555 In addition to TGF-β and IFN-γ, these supernatants contain oncostatin M, a glycoprotein produced by phorbol ester-stimulated U-937 human histiocytoma cells that acts as a GIF for A375 melanoma cells and other types of tumor cells, but not for normal human fibroblasts. However, oncostatin M is a multifunctional cytokine and is a potent natural mitogen for rabbit vascular smooth cells in culture.556 Oncostatin M is a major growth factor for AIDS-associated Kaposi’s sarcoma cells.557,558 Genomic cloning, sequence analysis, and expression of a cDNA coding for oncostatin M has been reported.559 Purified oncostatin M is a single chain polypeptide of 28 kDa that exerts a reversible cytostatic effect on A375 tumor cells. Binding sites for oncostatin M are present in various human and nonhuman tumor cell lines.560 Oncostatin M is structurally related to LIF and IL-6, and its physiological effects are mediated by the gp130 IL-6 signal transducer.561,562 Oncostatin M is internalized and degraded subsequently to binding. It is able to regulate the expression of proto-oncogenes such as c-myc, c-jun, and egr-1.563 The mechanism of oncostatin M action is associated with tyrosine phosphorylation of cellular proteins.
Roseburia intestinalis inhibits oncostatin M and maintains tight junction integrity in a murine model of acute experimental colitis
Published in Scandinavian Journal of Gastroenterology, 2019
Bei Tan, Weiwei Luo, Zhaohua Shen, Mengwei Xiao, Shuai Wu, Xiangrui Meng, Xing Wu, Zhenyu Yang, Li Tian, Xiaoyan Wang
Oncostatin M (OSM), which belongs to the IL-6 cytokine family, is produced largely by hematopoietic cells such as monocytes/macrophages, dendritic cells and T lymphocytes. OSM plays roles in tumor growth and invasiveness, metabolism and inflammation [14,15]. A recent study reports increased expression of OSM in inflamed intestinal tissue from patients with IBD, and that OSM expression is positively associated with failure of anti-TNF therapy [16]. Furthermore, some studies show that an abundance of certain intestinal microbiota (mainly Clostridiales) predicts responses to anti-TNF medications [17–19]. Current therapies for IBD include 5-aminosalicylates (e.g., mesalazine) and immunosuppressive drugs. As an increasing number of patients with IBD do not respond to these ‘classic’ treatments, anti-TNF agents have been introduced into clinical therapy [20,21]. However, up to 40% of patients do not respond to these agents [21]; therefore, a better understanding of mechanisms underlying resistance to anti-TNF medication is required.
Oncostatin M as a new diagnostic, prognostic and therapeutic target in inflammatory bowel disease (IBD)
Published in Expert Opinion on Therapeutic Targets, 2019
Sare Verstockt, Bram Verstockt, Séverine Vermeire
Given the high rate of primary and acquired resistance to current IBD treatments [7], novel drug targets and biomarkers stratifying patients toward a treatment strategy (top-down vs step-up) and toward a specific compound are eagerly awaited. Among those potential targets and biomarkers, oncostatin M (OSM) has gained a lot of interest in the past few years. Hence, this review aims to summarize the biology of OSM, its role in health and disease, its potential as diagnostic, prognostic and therapeutic biomarker in the field of IBD and how OSM might be a novel drug target in future.
Application of amniotic membrane in reconstructive urology; the promising biomaterial worth further investigation
Published in Expert Opinion on Biological Therapy, 2019
Jan Adamowicz, Shane Van Breda, Dominik Tyloch, Marta Pokrywczynska, Tomasz Drewa
Oncostatin M is a pleiotropic cytokine of the Il-6 family which promotes early wound healing by suppression of injury triggered inflammation and related local tissue destruction [50]. OM contained in AM should accelerate the reepithelization rate and encourage urothelium growth. Essential for the application in urological tissue engineering are reports describing OM as a potent activator of mesenchymal differentiation [51]. This phenomenon might be beneficial for smooth muscle layer regeneration.