TY - JOUR T1 - 14 The role of TILRR in vascular cell inflammation and development of atherosclerosis JF - Heart JO - Heart SP - e7 LP - e7 DO - 10.1136/heartjnl-2011-300920b.14 VL - 97 IS - 20 AU - M Neilan AU - J Boyle AU - A Lawrie AU - S Francis AU - D Haskard AU - E Qwarnstrom Y1 - 2011/10/15 UR - http://heart.bmj.com/content/97/20/e7.13.abstract N2 - 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. ER -