Article Text

Download PDFPDF

BAS/BSCR poster abstract
BAS/BSCR5 TILRR potentiates interleukin-1-induced anti-apoptosis
  1. Gemma Montagut Pino,
  2. Xiao Zhang,
  3. Eva E Qwarnstrom
  1. Cell Biology, Vascular Science, University of Sheffield, UK


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.

Statistics from

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.


  • Funding BHF and the BBSRC.