Article Text

PDF

BAS/BSCR poster abstract
BAS/BSCR41 Modulation of extracellular matrix protein expression by interleukin 1 in human cardiac myofibroblasts: regulation by p38 MAP kinase
  1. N A Turner,
  2. P Warburton,
  3. K E Porter
  1. Division of Cardiovascular and Neuronal Remodelling, Multidisciplinary Cardiovascular Research Centre (MCRC), University of Leeds, Leeds, UK

Abstract

The proinflammatory cytokine interleukin 1 (IL-1) elicits catabolic effects on the myocardial extracellular matrix (ECM) early after myocardial infarction but there is little understanding of its direct effects on cardiac myofibroblasts (CMF), a key cell type involved in the regulation of myocardial remodelling. We used a focused RT-PCR microarray to investigate the effects of IL-1 on expression of 41 ECM genes in CMF cultured from different patients, and explored the regulatory role of the p38 MAPK signalling pathway. IL-1 (10 ng/ml, 6 h) had only a minimal effect on mRNA expression of structural ECM proteins, including collagens, laminins, fibronectin and vitronectin. However, IL-1 induced marked increases in expression of several ECM proteases, including matrix metalloproteinases MMP-1 (collagenase-1), MMP-3 (stromelysin-1), MMP-9 (gelatinase-B) and MMP-10 (stromelysin-2). Conversely, IL-1 reduced mRNA expression of ADAMTS-1, a metalloproteinase that suppresses neovascularisation. IL-1 stimulated a small increase in expression of tissue inhibitor of metalloproteinases (TIMP)-1, but not TIMP-2. Data for MMPs 1, 2, 3, 9 and 10 and ADAMTS-1 were confirmed by quantitative real-time RT-PCR. IL-1 strongly activated the p38 MAPK pathway in human CMF, as determined by immunoblotting with phospho-specific antibodies. A p38 MAPK inhibitor (SB203580) reduced IL-1-induced mRNA expression of MMP-3, but did not affect expression of any of the other MMPs studied. SB203580 also markedly reduced ADAMTS-1 mRNA expression.

In summary, IL-1 induces a distinct pattern of ECM protease expression in human CMF, in part regulated by p38 MAPK, affirming the key role of IL-1 and CMF in postinfarction cardiac remodelling.

    Statistics from Altmetric.com

      Footnotes

      • Funding Funded by a British Heart Foundation project grant.

      Request permissions

      If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.