University of Hertfordshire

  • L. Moreno
  • S.K. McMaster
  • M. Paul-Clark
  • Louise Susan MacKenzie
  • N. Cartwright
  • T. Secher
  • V. Quesniaux
  • B. Ryffel
  • J.A. Mitchell
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Original languageEnglish
Article numberC057
Pages (from-to)48
JournalFundamental & Clinical Pharmacology
Journal publication date1 Aug 2008
Volume22
IssueS2
DOIs
Publication statusPublished - 1 Aug 2008
EventEPHAR 2008 Congress - Manchester, United Kingdom
Duration: 13 Jul 200817 Jul 2008

Abstract

Bacteria activate macrophages and vascular smooth muscle cells (VSMCs) resulting in induction of nitric oxide synthase (NOS)II activity. Here we show that the PPARc agonist rosiglitazone (rosi) increases the sensing of Gram positive bacteria by VSMCs but not macrophages via a CD36 dependent pathway. NOSII activity was increased in rat VSMCs by Gram positive S. aureus (3 · 108CFU/ml) or Gram negative E. coli (108 CFU/mL). Pre-treatment of cells with rosi increased NOSII activity in cells treated with S. aureus, but not E. Coli (Fig 1A), an effect prevented by the PPARc antagonist GW9962 (10-5 M; 91 ± 9% control) or a specific binding antibody to CD36 (99 ± 14%). CD36 levels in VSMCs were increased by rosi (by 8.7 ± 0.2 fold, n = 4). By contrast, rosi inhibited NOSII activity induced by bacteria in macrophages from wild type mice and CD36-/- mice (Fig 1B). S. aureus induced similarly hyporeactivity (mediated by NOSII) in vessels from wild type (not shown) or CD36-/- mice (Fig 1C).
These data reveal a mechanism by which PPARc agonists may propagate vascular
inflammation.

ID: 8137066