The type II "receptor" as a decoy target for interleukin 1 in polymorphonuclear leukocytes: Characterization of induction by dexamethasone and ligand binding properties of the released decoy receptor

Fabio Re, Marta Muzio, Marco De Rossi, Nadia Polentarutti, Judith G. Giri, Alberto Mantovani, Francesco Colotta

Research output: Contribution to journalArticlepeer-review

Abstract

Whereas the signaling function of the interleukin 1 (IL-1) receptor type I (IL-1R I) has been well documented, the type II "receptor" has been suggested to act as a decoy target for this cytokine. Since IL-1 may represent a key target of the immunomodulatory and antiinflammatory properties of glucocorticoids (GC), the aim of this study was to investigate the effects of dexamethasone (Dex) on IL-1R expression in human polymorphonuclear leukocytes (PMN), which express predominantly the type II molecule (IL-1R II). We found that Dex augments the levels of steady state transcripts encoding the IL-1R I and, most prominently, those of IL-1R II. Dex induced both transcripts via transcription-dependent mechanisms and by prolongation of the mRNAs half-lives. Inhibition of protein synthesis superinduced basal and Dex-augmented IL-1R II mRNA, whereas it completely inhibited the induction by Dex of IL-1R I transcripts. Induction of IL-1R II mRNA by Dex was associated with augmented membrane expression and release of the type II IL-1 binding molecule. This effect was mediated by the GC receptor. Other steroids (17β-estradiol, progesterone, and testosterone) were ineffective. The concentrations of IL-1α and IL-1 receptor antagonist required to displace the binding of IL-1β to the soluble form of the decoy molecule induced by Dex from PMN were, respectively, 100 and 2 times higher compared with IL-1β. The induction by Dex of the type II receptor, a decoy molecule for IL-1, may contribute to the immunosuppressive and antiinflammatory activities of Dex.

Original languageEnglish
Pages (from-to)739-743
Number of pages5
JournalJournal of Experimental Medicine
Volume179
Issue number2
Publication statusPublished - Feb 1 1994

ASJC Scopus subject areas

  • Immunology

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