%0 Journal Article
%T The new IL-1 family member IL-1F8 stimulates production of inflammatory mediators by synovial fibroblasts and articular chondrocytes
%A David Magne
%A Gaby Palmer
%A Jenny L Barton
%A Francoise M¨¦zin
%A Dominique Talabot-Ayer
%A Sylvette Bas
%A Trevor Duffy
%A Marcus Noger
%A Pierre-Andre Guerne
%A Martin JH Nicklin
%A Cem Gabay
%J Arthritis Research & Therapy
%D 2006
%I BioMed Central
%R 10.1186/ar1946
%X Until recently, the IL-1 family of cytokines included four members, with three having pro-inflammatory effects (IL-1¦Á, IL-1¦Â and IL-18) and the fourth member being an IL-1 receptor antagonist (IL-1Ra). IL-1 family members exert their effects through binding to receptors that belong to the IL-1 receptor (IL-1R) family. IL-1¦Á and IL-1¦Â bind to the type I IL-1 receptor (IL-1RI), resulting in recruitment of the IL-1 receptor accessory protein (IL-1RAcP), which is necessary for signal transduction. IL-1Ra negatively regulates IL-1 activity by competing with IL-1 for binding to IL-1RI. Binding of IL-1Ra to IL-1RI does not allow the recruitment of the accessory protein, and therefore it does not generate a signal (for review see [1]). IL-18 activity is mediated through its binding to other members of the same receptor family, namely IL-18 receptor (IL-18R) and the IL-18R accessory protein [2].Six new members of the IL-1 family were recently identified, primarily through the use of DNA database searches for homologues of IL-1 [3-10]. These proteins were named IL-1F5 to IL-1F10 [11]. In humans all of the new genes map to less than 300 kb of chromosome 2, where they are flanked by IL-1¦Á, IL-1¦Â and IL-1Ra. Sequence alignments and some physical data predict that the secondary structure of all of the new homologues is characterized by a 12-stranded ¦Â-trefoil structure shared with IL-1¦Á, IL-1¦Â and IL-1Ra [12]. IL-1F5 was recently characterized at high resolution [13].Expression patterns and the biological functions of the six new IL-1 family members have not yet been well characterized. It has been reported that IL-1F7 forms a complex with IL-18 binding protein, which might bind to and sequester IL-18R accessory protein, thus inhibiting the effects of IL-18 [14]. In addition, adenoviral overexpression of IL-1F7 in mouse was shown to have anti-tumour effects by an undefined mechanism, even though rodents appear to lack the IL-1F7 gene [15]. IL-1F10 has been described as a low affi
%U http://arthritis-research.com/content/8/3/R80