RAT HOMOLOG OF MOUSE INTERLEUKIN-1 RECEPTOR ACCESSORY PROTEIN - CLONING, LOCALIZATION AND MODULATION STUDIES

A protein which facilitates the binding between interleukin-l (IL-1) a nd the type I IL-1 receptor (designated as interleukin-l receptor acce ssory protein, IL-1RAcP) has recently been cloned in mouse cells. In t he present study, a rat homolog of the mouse IL-1RAcP was isolated fro m a rat superior cervical ganglion library. The deduced 570 amino acid sequences between rat and mouse IL-1RAcP have >95% sequence identity to each other with similar predicted signal peptide sequence (20 amino acids), extracellular domain (339 amino acids), a single transmembran e domain (24 amino acids) and a long intracellular domain (187 amino a cids). The rat IL-1RAcP has similar to 25% sequence identity to the ra t type I IL-1 receptor and a predicted extracellular domain with three immunoglobulin-like loops. RNase protection assays demonstrated that rat IL-1RAcP is expressed in both brain and peripheral tissues with th e highest densities present in liver and brain areas such as hypothala mus, cerebral cortex, hippocampus and cerebellum; significantly lower densities were present in lung and in immune tissues such as thymus an d spleen. The presence of IL-1RAcP in brain was confirmed by in situ h ybridization histochemical studies with a discrete localization presen t in the dentate gyrus of the hippocampus. The IL-1RAcP was down-regul ated in parallel with the type I IL-1 receptor in the liver following endotoxin treatment in rats. These data demonstrating the presence and modulation of a rat homolog of a mouse IL-1RAcP, which is highly expr essed in brain and peripheral tissues containing type I rat IL-1 recep tor, further suggest the importance of the interaction between the two proteins in rat in modulating the actions of IL-1. On the other hand, the presence of the IL-1RAcP in brain areas which show an absence of type I IL-1 receptors suggests additional functions for this protein i n the rat.