IL1 receptors

Two distinct IL-1 receptors have been identified as shown by the cloning studies of Sims and coworkers. Both receptors are members of the immunoglobulin superfamily. The type I receptor is an 80 kDa transmembrane protein, 552 amino acids long, with a single 22 amino acid transmembrane region and a long cytoplasmic tail of 213 amion acids. Its extracellular ligand-binding region consists of three immunoglob-ulin-like domains. The type II receptor is a 60 kDa protein and is similar to the type I receptor in its extracellular and transmembrane regions. The type II receptor has a short cytoplasmic tail of 29 amino acids and is incapable of signal transduction. The type II receptor actually competitively inhibits IL-1 activity by acting as a 'decoy' receptor for IL-1, and regulates the level of extracellular IL-1.

IL-1 acts on target cells by binding with high affinity (Kd of 10~10 m) to IL-1 type I receptors. Type I receptors are found on T cells, endothelial cells, hepatocytes, fibroblasts and keratinocytes, whereas type II receptors appear to have a more restricted distribution. Type II IL-1 receptors are the predominant receptor on B cells, monocytes and neutrophils. IL-lct, IL-1 £ and IL-lra show detectable affinity for both types of IL-1 receptors. However, IL-la binds preferentially with somewhat higher affinity to type I receptor and IL-1 (3 binds preferentially to type II receptor. IL-lra binds type I receptor with considerably higher affinity than it binds to type II 'decoy' receptor, and it can block the binding to type I receptor and consequent biological activities of both IL-la and IL-1 p. However, a 10- to 500-fold excess of IL-lra may be necessary to achieve a 50% inhibition of the biological effects of IL-1 in vitro. Pro-IL-l(3 does not bind to type I receptor and therefore has no detectable biological activity. The receptor binding affinity and biological activities of the pro and mature forms of IL-la appear indistinguishable. Despite the low number of type I receptors (200 per cell), all biological responses of IL-1 are mediated by type I receptors. A receptor occupancy of less than 5% per cell is sufficient to activate cells. These data suggest that a major amplification of IL-1 signal must occur after IL-1 ligand/receptor interaction. Recently, Greenfeder and colleagues identified an IL-1 receptor accessory protein which is the putative signal transducing subunit of the IL-1 receptor complex. IL-1 receptor accessory protein does not bind IL-1 directly but forms a complex with type I IL-1 receptor after it is bound by either IL-la or IL-1(3 but not IL-lra.

Expression of both type I and type II IL-1 receptors is regulated to control inflammation and immune responses. Dexamethasone, PGE2 and cytokines with known anti-inflammatory properties, such as IL-4, IL-10, IL-13 and TGF|3, can increase receptor expression and shedding from cell membrane. The extracellular domain of both type I and type II receptor is shed by activated neutrophils and monocytes and the solubilized shed receptor binds and inhibits IL-1 p functions. Recently, it was shown that vaccinia and cowpox viruses encode a protein with 30% sequence homology to the soluble type II IL-1 receptor. The presence of this protein counteracts the host inflammatory response to these viruses because viruses genetically engineered to lack these genes become less pathogenic.

How To Bolster Your Immune System

How To Bolster Your Immune System

All Natural Immune Boosters Proven To Fight Infection, Disease And More. Discover A Natural, Safe Effective Way To Boost Your Immune System Using Ingredients From Your Kitchen Cupboard. The only common sense, no holds barred guide to hit the market today no gimmicks, no pills, just old fashioned common sense remedies to cure colds, influenza, viral infections and more.

Get My Free Audio Book

Post a comment