Logo of pnasPNASInfo for AuthorsSubscriptionsAboutThis Article
Proc Natl Acad Sci U S A. Feb 28, 1995; 92(5): 1714–1718.
PMCID: PMC42590

Soluble type II interleukin 1 (IL-1) receptor binds and blocks processing of IL-1 beta precursor and loses affinity for IL-1 receptor antagonist.

Abstract

Two IL-1 receptors have been identified, termed type I and type II. The extracellular domain of the type II IL-1 receptor is released from certain cells and can function as a specific inhibitor of IL-1 beta activity. We assessed the ligand-binding properties of the type II membrane-bound and soluble IL-1 receptor (sIL-1R) from the human B cell line Raji by competition. Upon release, the affinity of sIL-1R for IL-1 alpha and IL-1 beta remained constant, and both soluble and cell surface IL-1 receptors bound to the same regions on the IL-1 beta molecule as defined by binding of a series of IL-1 beta mutant molecules. However, the affinity of sIL-1R for the IL-1 receptor antagonist (IL-1ra) decreased by a factor of 2000 when compared with the cell surface receptor. Type II sIL-1R and IL-1ra had an additive effect in inhibiting the binding of IL-1 beta to cell surface IL-1 receptors. In contrast, the combination of recombinant type 1 sIL-1R with IL-1ra abrogated the inhibition seen with each of the individual agents alone. The type II cell surface IL-1 receptor failed to bind the biologically inactive IL-1 beta precursor molecule, but binding to the IL-1 beta precursor was observed on cellular release of the receptor; this was confirmed with 35S-labeled IL-1 beta. Binding of IL-1 beta precursor by sIL-1R inhibited the precursor's ability to be processed to the mature, biologically active 17-kDa species. These observations suggest that the type II sIL-1R inhibits IL-1 beta at two steps, by preventing processing of propeptide and by blocking the interaction of mature IL-1 beta with type I IL-1 receptor. In addition, type II sIL-1R does not interfere with inhibition mediated by IL-1ra.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.3M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Dinarello CA. Interleukin-1 and interleukin-1 antagonism. Blood. 1991 Apr 15;77(8):1627–1652. [PubMed]
  • Hannum CH, Wilcox CJ, Arend WP, Joslin FG, Dripps DJ, Heimdal PL, Armes LG, Sommer A, Eisenberg SP, Thompson RC. Interleukin-1 receptor antagonist activity of a human interleukin-1 inhibitor. Nature. 1990 Jan 25;343(6256):336–340. [PubMed]
  • Hazuda DJ, Lee JC, Young PR. The kinetics of interleukin 1 secretion from activated monocytes. Differences between interleukin 1 alpha and interleukin 1 beta. J Biol Chem. 1988 Jun 15;263(17):8473–8479. [PubMed]
  • Mosley B, Urdal DL, Prickett KS, Larsen A, Cosman D, Conlon PJ, Gillis S, Dower SK. The interleukin-1 receptor binds the human interleukin-1 alpha precursor but not the interleukin-1 beta precursor. J Biol Chem. 1987 Mar 5;262(7):2941–2944. [PubMed]
  • Cerretti DP, Kozlosky CJ, Mosley B, Nelson N, Van Ness K, Greenstreet TA, March CJ, Kronheim SR, Druck T, Cannizzaro LA, et al. Molecular cloning of the interleukin-1 beta converting enzyme. Science. 1992 Apr 3;256(5053):97–100. [PubMed]
  • Thornberry NA, Bull HG, Calaycay JR, Chapman KT, Howard AD, Kostura MJ, Miller DK, Molineaux SM, Weidner JR, Aunins J, et al. A novel heterodimeric cysteine protease is required for interleukin-1 beta processing in monocytes. Nature. 1992 Apr 30;356(6372):768–774. [PubMed]
  • Hazuda DJ, Strickler J, Kueppers F, Simon PL, Young PR. Processing of precursor interleukin 1 beta and inflammatory disease. J Biol Chem. 1990 Apr 15;265(11):6318–6322. [PubMed]
  • Sims JE, March CJ, Cosman D, Widmer MB, MacDonald HR, McMahan CJ, Grubin CE, Wignall JM, Jackson JL, Call SM, et al. cDNA expression cloning of the IL-1 receptor, a member of the immunoglobulin superfamily. Science. 1988 Jul 29;241(4865):585–589. [PubMed]
  • McMahan CJ, Slack JL, Mosley B, Cosman D, Lupton SD, Brunton LL, Grubin CE, Wignall JM, Jenkins NA, Brannan CI, et al. A novel IL-1 receptor, cloned from B cells by mammalian expression, is expressed in many cell types. EMBO J. 1991 Oct;10(10):2821–2832. [PMC free article] [PubMed]
  • Stylianou E, O'Neill LA, Rawlinson L, Edbrooke MR, Woo P, Saklatvala J. Interleukin 1 induces NF-kappa B through its type I but not its type II receptor in lymphocytes. J Biol Chem. 1992 Aug 5;267(22):15836–15841. [PubMed]
  • Sims JE, Gayle MA, Slack JL, Alderson MR, Bird TA, Giri JG, Colotta F, Re F, Mantovani A, Shanebeck K, et al. Interleukin 1 signaling occurs exclusively via the type I receptor. Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):6155–6159. [PMC free article] [PubMed]
  • Symons JA, Eastgate JA, Duff GW. Purification and characterization of a novel soluble receptor for interleukin 1. J Exp Med. 1991 Nov 1;174(5):1251–1254. [PMC free article] [PubMed]
  • Eastgate JA, Symons JA, Duff GW. Identification of an interleukin-1 beta binding protein in human plasma. FEBS Lett. 1990 Jan 29;260(2):213–216. [PubMed]
  • Symons JA, Eastgate JA, Duff GW. A soluble binding protein specific for interleukin 1 beta is produced by activated mononuclear cells. Cytokine. 1990 May;2(3):190–198. [PubMed]
  • Colotta F, Re F, Muzio M, Bertini R, Polentarutti N, Sironi M, Giri JG, Dower SK, Sims JE, Mantovani A. Interleukin-1 type II receptor: a decoy target for IL-1 that is regulated by IL-4. Science. 1993 Jul 23;261(5120):472–475. [PubMed]
  • Symons JA, Duff GW. A soluble form of the interleukin-1 receptor produced by a human B cell line. FEBS Lett. 1990 Oct 15;272(1-2):133–136. [PubMed]
  • Giri JG, Newton RC, Horuk R. Identification of soluble interleukin-1 binding protein in cell-free supernatants. Evidence for soluble interleukin-1 receptor. J Biol Chem. 1990 Oct 15;265(29):17416–17419. [PubMed]
  • Simon PL, Kumar V, Lillquist JS, Bhatnagar P, Einstein R, Lee J, Porter T, Green D, Sathe G, Young PR. Mapping of neutralizing epitopes and the receptor binding site of human interleukin 1 beta. J Biol Chem. 1993 May 5;268(13):9771–9779. [PubMed]
  • Joseph-Liauzun E, Leplatois P, Legoux R, Guerveno V, Marchese E, Ferrara P. Human recombinant interleukin-1 beta isolated from Escherichia coli by simple osmotic shock. Gene. 1990 Feb 14;86(2):291–295. [PubMed]
  • Krasney PA, Young PR. Further aspects of IL-1 beta secretion revealed by transfected monkey kidney cells. Cytokine. 1992 Mar;4(2):134–143. [PubMed]
  • Lillquist JS, Simon PL, Summers M, Jonak Z, Young PR. Structure-activity studies of human IL-1 beta with mature and truncated proteins expressed in Escherichia coli. J Immunol. 1988 Sep 15;141(6):1975–1981. [PubMed]
  • Cheng Y, Prusoff WH. Relationship between the inhibition constant (K1) and the concentration of inhibitor which causes 50 per cent inhibition (I50) of an enzymatic reaction. Biochem Pharmacol. 1973 Dec 1;22(23):3099–3108. [PubMed]
  • Priestle JP, Schär HP, Grütter MG. Crystal structure of the cytokine interleukin-1 beta. EMBO J. 1988 Feb;7(2):339–343. [PMC free article] [PubMed]
  • Mosley B, Dower SK, Gillis S, Cosman D. Determination of the minimum polypeptide lengths of the functionally active sites of human interleukins 1 alpha and 1 beta. Proc Natl Acad Sci U S A. 1987 Jul;84(13):4572–4576. [PMC free article] [PubMed]
  • Labriola-Tompkins E, Chandran C, Kaffka KL, Biondi D, Graves BJ, Hatada M, Madison VS, Karas J, Kilian PL, Ju G. Identification of the discontinuous binding site in human interleukin 1 beta for the type I interleukin 1 receptor. Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11182–11186. [PMC free article] [PubMed]
  • Young PR, Sylvester D. Cloning of rabbit interleukin-1 beta: differential evolution of IL-1 alpha and IL-1 beta proteins. Protein Eng. 1989 May;2(7):545–551. [PubMed]
  • Slack J, McMahan CJ, Waugh S, Schooley K, Spriggs MK, Sims JE, Dower SK. Independent binding of interleukin-1 alpha and interleukin-1 beta to type I and type II interleukin-1 receptors. J Biol Chem. 1993 Feb 5;268(4):2513–2524. [PubMed]
  • Granowitz EV, Clark BD, Mancilla J, Dinarello CA. Interleukin-1 receptor antagonist competitively inhibits the binding of interleukin-1 to the type II interleukin-1 receptor. J Biol Chem. 1991 Aug 5;266(22):14147–14150. [PubMed]
  • Dower SK, Wignall JM, Schooley K, McMahan CJ, Jackson JL, Prickett KS, Lupton S, Cosman D, Sims JE. Retention of ligand binding activity by the extracellular domain of the IL-1 receptor. J Immunol. 1989 Jun 15;142(12):4314–4320. [PubMed]
  • Alcamí A, Smith GL. A soluble receptor for interleukin-1 beta encoded by vaccinia virus: a novel mechanism of virus modulation of the host response to infection. Cell. 1992 Oct 2;71(1):153–167. [PubMed]
  • Ray CA, Black RA, Kronheim SR, Greenstreet TA, Sleath PR, Salvesen GS, Pickup DJ. Viral inhibition of inflammation: cowpox virus encodes an inhibitor of the interleukin-1 beta converting enzyme. Cell. 1992 May 15;69(4):597–604. [PubMed]
  • Antin JH, Weinstein HJ, Guinan EC, McCarthy P, Bierer BE, Gilliland DG, Parsons SK, Ballen KK, Rimm IJ, Falzarano G, et al. Recombinant human interleukin-1 receptor antagonist in the treatment of steroid-resistant graft-versus-host disease. Blood. 1994 Aug 15;84(4):1342–1348. [PubMed]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

  • Cited in Books
    Cited in Books
    PubMed Central articles cited in books
  • Gene
    Gene
    Gene links
  • GEO Profiles
    GEO Profiles
    Related GEO records
  • HomoloGene
    HomoloGene
    HomoloGene links
  • Pathways + GO
    Pathways + GO
    Pathways, annotations and biological systems (BioSystems) that cite the current article.
  • Protein
    Protein
    Published protein sequences
  • PubMed
    PubMed
    PubMed citations for these articles
  • Substance
    Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...