Bacterial lipopolysaccharide causes rapid shedding, followed by inhibition of mRNA expression, of the IL-1 type II receptor, with concomitant up-regulation of the type I receptor and induction of incompletely spliced transcripts

Giselle Penton-Rol, Simone Orlando, Nadia Polentarutti, Sergio Bernasconi, Marta Muzio, Martino Introna, Alberto Mantovani

Research output: Contribution to journalArticlepeer-review

Abstract

The IL-1 type I receptor (IL-1RI) is part of a signaling complex together with the IL-1R accessory protein, whereas available information is consistent with a 'decoy' model of function for the IL-1 type II receptor (IL-1RII). The present study was designed to investigate the effect of bacterial LPS on IL-1R in human monocytes. LPS causes rapid release of the IL-1RII, an effect blocked by a metalloprotease inhibitor. Subsequently, LPS- treated monocytes showed a drastic reduction of IL-1RII mRNA. In contrast, LPS induced IL-1RI and, to a lesser extent, IL-1AcP expression. LPS-induced augmented expression of the canonical 5-kb IL-1RI mRNA was accompanied by the appearance of 2.4-kb IL-1RI transcripts. The use of probes representative of different regions of the IL-1RI mRNA, as well as cDNA cloning, revealed that the 2.4-kb inducible band includes incompletely spliced, polyadenylated transcripts potentially encoding truncated versions of the receptor. The observation that the prototypic proinflammatory molecule LPS has divergent effects on IL-1Rs, with inhibition of IL-1RII and stimulation of IL-1RI and IL-1R accessory protein, is consistent with the view that these molecules subserve opposite functions in the pathophysiology of the IL-1 system. The rapid shedding of IL-1RII by monocytes early in recruitment may serve to buffer the systemic action of IL-1 leaking from sites of inflammation. This early event, followed by prolonged inhibition of IL-1RII expression and up- regulation of IL-1RI, may render monocytes more responsive to IL-1 at sites of inflammation.

Original languageEnglish
Pages (from-to)2931-2938
Number of pages8
JournalJournal of Immunology
Volume162
Issue number5
Publication statusPublished - Mar 1 1999

ASJC Scopus subject areas

  • Immunology

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