The interleukin 1 receptor

Abstract

The diverse biological activities of interleukin 1 (IL-1) have attracted interest from a wide range of biological disciplines ~ After systemic injection into a variety of animals, it seems that IL-1 affects nearly every organ system. Interested parties fall into two groups: those studying the potential beneficial effects of IL-1 on host defense mechanisms, particularly the hemopoietic stem cell, and those looking at ways to block the production and/or activity of IL-1 since many of its biological activi- ties are associated with a pathogenic disease process such as tissue degradation in arthritis and diabetes. Some groups are now preparing to use IL-1 in humans to bolster the stem cell's reactivity to colony-stimulating factors (CSFs)I while other groups in clinical trials with claims that new drugs for pain and arLhriti.~ work by reducing production of IL-1. No doubt the cloning of an IL-1 receptor molecule is of vital importance to both areas of investigation. Cloning of the 80 kDa IL-l-binding protein An 80 kDa IL-l-specific binding protein has been observed on a variety of cell lines 2-7. It recognized both IL-loL and IL-113. Treatment of this 80 kDa protein with glycanases reduces its size to about 65 kDa, indicating that the variability in molecular weight reported by several investigators may be due to differential glycosy- lation. In addition, some experiments using tunicamycin and plant lectins suggest that the glycosylation sites of the 80 kDa IL-1 receptor may play a role in receptor affinity a. The 80 kDa IL-l-binding protein has been purified to homogeneity from the murine cell line EL4 6.1 C10 and the 26 amino-terminal amino acids have beer, determinedg~ Using a direct in-situ binding assay, the 80 kDa IL-l-binding protein has been cloned 1° and the amino acid sequence derived from the cDNA matches that of the purified protein. The actual molecular weight of the 80 kDa IL-l-binding protein is 64.598 kDa. This protein, which is not homologous to other proteins presently reported in the various databases, is the IL-1 receptor. The question remains whether this is the sole IL-1 receptor responsible for the multitude of biological activities of IL-1. If other IL-l-binding proteins exist, do they function alone or in combination with the 80 kDa protein to form the IL-1 receptor? The II.-1 receptor is a member of the immunoglobulin superfamily Several groups have been actively involved in studies on the binding of IL-1 to the plasma membranes of various cells and cell lines. The report by Sims etal. ~° is a welcome addition to these studies and their effo~-ts will certainly help to advance the :lnderstanding of the biology of IL-1. The murine IL-1 receptor is comprised of three domains: a 319 amino acid ~-xtracellular portion, a 21 amino acid hydrophobic trar,~,membrane segment, and a 217 amino acid piece probably located in the cytoplasm. The sequence of the cytoplasmic segment does not show any similarities to those of protein Departments of Medicine, Pediatrics and Physiology, Tufts University School of Medicine and New England Medical Center, Boston, MA 0211 I, USA.