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14 The role of TILRR in vascular cell inflammation and development of atherosclerosis
  1. M Neilan1,
  2. J Boyle2,
  3. A Lawrie1,
  4. S Francis1,
  5. D Haskard2,
  6. E Qwarnstrom1
  1. 1Cardiovascular Science, University of Sheffield, UK
  2. 2Vascular Sciences, National Heart and Lung Institute, Imperial College London, UK

Abstract

Inflammatory responses are induced by members of the Toll-like and Interleukin-1 receptor family. We have identified an IL-1RI (interleukin-1 receptor type I) co-receptor, TILRR, (toll-like and IL-1 receptor regulator), which associates with the signalling receptor and potentiates activation of NF-kB and inflammatory responses.1 Earlier studies have confirmed expression and function of TILRR in both inflammatory and vascular cells. More recent experiments have demonstrated a pronounced increase in TILRR expression in the atherosclerotic plaque using mouse models (ApoE−/− and LDLR−/−). The current studies focus on determining the role of TILRR in development of atherosclerosis, specifically in relation to its impact on IL-1-induced responses. Immuno-histochemical studies have demonstrated the presence of TILRR in sections of vascular lesions from human samples, correlating with areas of IL-1RI activity. In experiments using ApoE/IL-1RI double knockouts, the high fat diet had only minor impact on the level of TILRR expression in vascular tissue. We have confirmed specificity of the co-receptor to IL-RI by demonstrating that other receptor systems controlling vascular inflammation, such as TNFR, are insensitive to TILRR expression over a range of ligand concentrations. Ongoing studies use custom anti-TILRR antibodies to test effects of blocking TILRR association with IL-1RI on development of atherosclerosis. Antibodies are injected into fat-fed ApoE−/− mice, and plaque formation determined using computer based imaging and semi-quantitative scoring.

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Footnotes

  • Funding Supported by BHF and BBSRC.

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