BAS/BSCR51 Control of vascular cell inflammatory responses through TILRR, an interleukin 1 co-receptor

Abstract

Inflammatory responses are induced by members of the Toll-Like and interleukin (IL)-1 receptor family and controlled by NF-κB.We have identified an IL-1RI co-receptor, TILRR, which potentiates activation of NF-κB and inflammatory responses. We show that induction of amplification depends on formation of a TILRR-containing receptor complex, which imparts enhanced recruitment of the MyD88 adaptor to the signalling receptor IL-1RI, and induction of Ras-dependent amplification of NF-κB.1We have confirmed expression of TILRR in vascular cells and have demonstrated a correlation of the level of TILRR expression with the level of NF-κB activity and inflammatory responses, induced by IL-1 stimulation and by mechanotransduction.Our recent studies have demonstrated expression of TILRR in vascular endothelial cells using immunohistochemistry. Sections of perfusion-fixed, paraffin-embedded vascular tissue were stained using a specific rabbit polyclonal anti-TILRR antibody, followed by incubation with a biotinylated goat anti-rabbit antibody. Ongoing studies using wild type and ApoE−/− mice are designed to assess the impact of diet on TILRR expression and on its association with the signalling partner IL-1RI.