Oncostatin M induces interleukin-6 and cyclooxygenase-2 expression in human vascular smooth muscle cells : synergy with interleukin-1beta.

Oncostatin M (OSM), a cytokine first identified from activated monocytes and T lymphocytes, is one of the most potent autocrine growth factor for AIDS and Kaposi's sarcoma. Little is known about the effects of OSM on normal vascular cells. We thus exposed human aortic smooth muscle cells (hASMCs) to OSM, examined cell proliferation and morphology, and determined interleukin-6 (IL-6) and cyclooxygenase-2 (COX-2) expression. OSM had a weak antiproliferative effect. After a 4-day incubation with 100 ng/mL OSM, cell count decreased to 69+/-3% of control. However, OSM induced striking changes in hASMC morphology, characterized by a polyclonal shape, in contrast to the spindle morphological feature of control hASMCs. OSM stimulated the release of IL-6 by hASMCs in a dose-dependent way; after a 48-hour exposure, values were 8.5+/-0.7, 29.7+/-3.5, 50.9+/-4.4, and 73.8+/-7.6x10(3) U/mL (n=6) at OSM concentrations of 0, 1, 10, and 100 ng/mL, respectively. OSM induced marked expression of COX-2 protein and mRNA. Leukemia inhibitory factor had no effect on hASMCs, indicating that OSM effects on hASMCs were mediated by the OSM type II receptor and not by the leukemia inhibitory factor receptor. OSM used the JAK/STAT signaling pathway, as demonstrated by rapid phosphorylation of JAK1 and specific activation of STAT1. Interestingly, OSM acted in synergy with IL-1beta on IL-6 production and COX-2 expression. In conclusion, OSM is a novel regulator of human smooth muscle cell functions, acting in concert with IL-1beta, and OSM may play a role in major vascular diseases such as atherosclerosis.

[1]  J. Ritz,et al.  Fludarabine-induced immunosuppression is associated with inhibition of STAT1 signaling , 1999, Nature Medicine.

[2]  N. Bazan,et al.  Budesonide epimer R or dexamethasone selectively inhibit platelet-activating factor-induced or interleukin 1beta-induced DNA binding activity of cis-acting transcription factors and cyclooxygenase-2 gene expression in human epidermal keratinocytes. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[3]  S. Chevalier,et al.  Regulation of interleukin 6 expression by cardiotrophin 1. , 1997, Cytokine.

[4]  A. Weyrich,et al.  Oncostatin M is a proinflammatory mediator. In vivo effects correlate with endothelial cell expression of inflammatory cytokines and adhesion molecules. , 1997, The Journal of clinical investigation.

[5]  C. Guillet,et al.  Signaling of Type II Oncostatin M Receptor* , 1997, The Journal of Biological Chemistry.

[6]  J. Maclouf,et al.  Regulation of the expression of cyclooxygenase-2 by nitric oxide in rat peritoneal macrophages. , 1997, Journal of immunology.

[7]  E. Wijelath,et al.  Oncostatin M induces basic fibroblast growth factor expression in endothelial cells and promotes endothelial cell proliferation, migration and spindle morphology. , 1997, Journal of cell science.

[8]  D. Friend,et al.  Dual Oncostatin M (OSM) Receptors , 1996, The Journal of Biological Chemistry.

[9]  J. Pan,et al.  Interleukin 4 or oncostatin M induces a prolonged increase in P- selectin mRNA and protein in human endothelial cells , 1996, The Journal of experimental medicine.

[10]  B. Nickoloff,et al.  Charting a new course through the chaos of KS (Kaposi's sarcoma) , 1996, The American journal of pathology.

[11]  J. Maclouf,et al.  Involvement of tyrosine kinases in the induction of cyclo-oxygenase-2 in human endothelial cells. , 1995, The Biochemical journal.

[12]  J. Auwerx,et al.  Fibrates increase human apolipoprotein A-II expression through activation of the peroxisome proliferator-activated receptor. , 1995, The Journal of clinical investigation.

[13]  D. Levy,et al.  Thrombopoietin activates a STAT5‐like factor in hematopoietic cells. , 1995, The EMBO journal.

[14]  A. Tedgui,et al.  Increased production of tumor necrosis factor and interleukin-6 by arterial wall of aged rats. , 1995, The American journal of physiology.

[15]  B. Ensoli,et al.  Cytokines from activated T cells induce normal endothelial cells to acquire the phenotypic and functional features of AIDS-Kaposi's sarcoma spindle cells. , 1995, The Journal of clinical investigation.

[16]  R. Law,et al.  Oncostatin-M is an autocrine growth factor in Kaposi's sarcoma. , 1994, The American journal of pathology.

[17]  J. Maclouf,et al.  Regulation of cyclooxygenase-2 expression in aortic smooth muscle cells. , 1994, Arteriosclerosis and thrombosis : a journal of vascular biology.

[18]  S. Dower,et al.  Oncostatin M and leukemia inhibitory factor trigger overlapping and different signals through partially shared receptor complexes. , 1994, The Journal of biological chemistry.

[19]  S. Higuchi,et al.  NS-398, a new anti-inflammatory agent, selectively inhibits prostaglandin G/H synthase/cyclooxygenase (COX-2) activity in vitro. , 1994, Prostaglandins.

[20]  J. Maclouf,et al.  Demonstration of an inducible cyclooxygenase in human endothelial cells using antibodies raised against the carboxyl-terminal region of the cyclooxygenase-2. , 1993, The Journal of biological chemistry.

[21]  M. Dohadwala,et al.  Exogenous tat protein activates human endothelial cells [see comments] , 1993 .

[22]  A. Nel,et al.  Oncostatin-M stimulates tyrosine protein phosphorylation in parallel with the activation of p42MAPK/ERK-2 in Kaposi's cells. Evidence that this pathway is important in Kaposi cell growth. , 1993, The Journal of clinical investigation.

[23]  David A Jones,et al.  Molecular cloning of human prostaglandin endoperoxide synthase type II and demonstration of expression in response to cytokines. , 1993, The Journal of biological chemistry.

[24]  P. Kiener,et al.  Oncostatin M is a mitogen for rabbit vascular smooth muscle cells. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[25]  P. Linsley,et al.  Oncostatin M as a potent mitogen for AIDS-Kaposi's sarcoma-derived cells. , 1992, Science.

[26]  J. Liu,et al.  Regulation of IL-6 expression by oncostatin M. , 1991, Journal of immunology.

[27]  T. Rose,et al.  Oncostatin M is a member of a cytokine family that includes leukemia-inhibitory factor, granulocyte colony-stimulating factor, and interleukin 6. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[28]  T. Hirano,et al.  AIDS Kaposi sarcoma-derived cells produce and respond to interleukin 6. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[29]  L. Sachs,et al.  Pattern of interleukin 6 gene expression in vivo suggests a role for this cytokine in angiogenesis. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[30]  P. Libby,et al.  Proliferating or interleukin 1-activated human vascular smooth muscle cells secrete copious interleukin 6. , 1990, The Journal of clinical investigation.

[31]  P. Linsley,et al.  Regulation of cell growth by recombinant oncostatin M. , 1990, Growth factors.

[32]  S. Nakamura,et al.  AIDS-Kaposi's sarcoma-derived cells express cytokines with autocrine and paracrine growth effects. , 1989, Science.

[33]  P. Libby,et al.  Comparative analysis of cytokine induction in human vascular endothelial and smooth muscle cells. , 1989, Lymphokine research.

[34]  P. Libby,et al.  Interleukin 1: a mitogen for human vascular smooth muscle cells that induces the release of growth-inhibitory prostanoids. , 1988, The Journal of clinical investigation.

[35]  H. Marquardt,et al.  Purification and characterization of cytostatic lymphokines produced by activated human T lymphocytes. Synergistic antiproliferative activity of transforming growth factor beta 1, interferon-gamma, and oncostatin M for human melanoma cells. , 1987, Journal of immunology.

[36]  M. Shibuya,et al.  Genistein, a specific inhibitor of tyrosine-specific protein kinases. , 1987, The Journal of biological chemistry.

[37]  P. Lansdorp,et al.  Production of hybridoma growth factor by human monocytes , 1987, European journal of immunology.

[38]  W. Rutter,et al.  Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. , 1979, Biochemistry.

[39]  F.,et al.  Exogenous tat Protein Activates Human Endothelial Cells , 2022 .