Oncostatin M and TLR-4 Ligand Synergize to Induce MCP-1, IL-6, and VEGF in Human Aortic Adventitial Fibroblasts and Smooth Muscle CellsReportar como inadecuado

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Mediators of InflammationVolume 2013 2013, Article ID 317503, 14 pages

Research Article

McMaster Immunology Research Centre, Department of Pathology and Molecular Medicine, McMaster University, ON, Canada L8S 4K1

Department of Biochemistry and Biomedical Sciences, Thrombosis and Atherosclerosis Research Institute, David Braley Cardiac, Vascular and Stroke Research Institute, McMaster University, Canada

Received 30 April 2013; Revised 7 September 2013; Accepted 10 September 2013

Academic Editor: Ronald Gladue

Copyright © 2013 David Schnittker et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Accumulating evidence suggests that adventitial fibroblasts play a significant role in contributing to inflammation of the arterial wall and pathogenesis of atherosclerosis. The effects of gp130 cytokines on these cells including oncostatin M-OSM and IL-6, some of which have been implicated in atherosclerosis, are currently unknown. Experiments were performed to determine whether gp130 cytokines regulate human aortic adventitial fibroblasts HAoAFs or smooth muscle cells HAoSMCs alone or in context of TLR-4 ligands also implicated in atherosclerosis. HAoAFs and HAoSMCs were stimulated with LPS and-or one of OSM, IL-6, IL-11, IL-31, or LIF. ELISAs performed on cell supernatants showed that stimulation with OSM alone caused increased MCP-1, IL-6, and VEGF levels. When combined, LPS and OSM synergized to increase MCP-1, IL-6, VEGF protein, and mRNA expression as assessed by qRT-PCR, in both HAoAFs and HAoSMCs, while LPS-induced IL-8 levels were reduced. Such effects were not observed with other gp130 cytokines. Signalling pathways including STATs, MAPKinases, and NFκB were activated, and LPS induced steady state mRNA levels of the OSM receptor chains OSMRβ and gp130. The results suggest that OSM is able to synergize with TLR-4 ligands to induce proinflammatory responses by HAoAFs and HAoSMCs, supporting the notion that OSM regulation of these cells contributes to the pathogenesis of atherosclerosis.

Autor: David Schnittker, Karen Kwofie, Ali Ashkar, Bernardo Trigatti, and Carl D. Richards

Fuente: https://www.hindawi.com/


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