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Heart 96:e13-e14 doi:10.1136/hrt.2010.205781.16
  • BSCR Spring 2010 Meeting Abstracts
  • BAS/BSCR poster abstract

BAS/BSCR5 TILRR potentiates interleukin-1-induced anti-apoptosis

  1. Eva E Qwarnstrom
  1. Cell Biology, Vascular Science, University of Sheffield, UK

    Abstract

    The pathogenesis of atherosclerosis is determined, in part, by inflammatory responses, induced through members of the Toll-like and interleukin (IL)-1 receptor family and controlled by NF-κB. We have identified a novel IL-1RI co-receptor, TILRR, which enhances the IL-1-induced activation of NF-κB by increasing receptor-expression enhanced recruitment of the MyD88 adaptor during activation.1 Here we investigate the role of TILRR on the anti-apoptotic effects controlled by NF-κB. The results showed that TILRR reduces caspase-3 activity and enhances IL-1-induced phosphorylation of AKT. Alanine scanning mutagenesis of the IL-1 receptor TIR domain demonstrated that TILRR amplifies inflammatory responses through the membrane proximal part of the cytoplasmic portion, the so-called box 1, while the anti-apoptotic response is regulated through the central portion of the TIR domain, the so-called box 2. Similarly, alanine scanning mutagenesis of the TILRR core protein, targeting conserved residues with predicted effects on secondary structure, demonstrated distinct control of inflammatory and anti-apoptotic intermediates. These results demonstrate that TILRR amplification involves selective control of NF-κB-regulated inflammatory and anti-apoptotic responses, and are consistent with induction of discrete conformational changes in the IL-1 receptor complex through TILRR association.

    Footnotes

    • Funding BHF and the BBSRC.