Regulated expression and release of the IL-1 decoy receptor in human mononuclear phagocytes

Francesco Colotta, Simona Saccani, Judith G. Giri, Steven K. Dower, John E. Sims, Martino Introna, Alberto Mantovani

Research output: Contribution to journalArticlepeer-review

Abstract

The aim of this study was to investigate the expression and release of the IL-1 type II decoy receptor (R) in mononuclear phagocytes, which play a central role in immune and chronic inflammatory reactions. Human monocytes expressed both type I and type II R transcripts, the latter being two- to threefold more represented. By cross-linking and Ab blocking, the predominant surface IL-1-binding molecule was the decoy RII. IL-4, IL-13, and dexamethasone induced RI and RII transcripts and augmented the number of IL- 1-binding sites with no modification of K(d) values. The induced surface receptor was identified as the decoy RII. These stimuli induced the release of a soluble R with a m.w. of approximately 60 kDa, of which N-glycosylation contributed 22 kDa compared with 45 kDa released from polymorphonuclear leukocytes, of which N-glycosylation contributed 15 kDa. IL-13 and dexamethasone induced a release of 24 ng/ml/2 x 107 cells (from 8.7 to 43.2 ng/ml) and 25.6 ng/ml/2 x 107 cells (from 9.7 to 36.8 ng/ml) of decoy RII in 18 h, respectively (six donors). Thus, for instance, IL-13-treated (18 h) cells expressed 3.5 x 103 sites/cell and released 12 x 103 decoy RII/cell. The released decoy RII from monocytes bound IL-1α and IL-1 receptor antagonist 30- and 2-fold less avidly than IL-1β, respectively. In vitro- matured, monocyte-derived macrophages showed higher levels of surface expression and release of the IL-1 decoy RII. The results show that, on exposure to diverse molecules with anti-inflammatory properties, mononuclear phagocytes express and release copious amounts of a novel version of the soluble IL-1 decoy RII.

Original languageEnglish
Pages (from-to)2534-2541
Number of pages8
JournalJournal of Immunology
Volume156
Issue number7
Publication statusPublished - Apr 1 1996

ASJC Scopus subject areas

  • Immunology

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