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.
Statistics from Altmetric.com
Funding Supported by BHF and BBSRC.
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.