Characterization of type II intracellular IL-1 receptor antagonist (IL-1ra3): A depot IL-1ra

Marta Muzio, Nadia Polentarutti, Fabio Facchetti, Giuseppe Peri, Andrea Doni, Marina Sironi, Pietro Transidico, Mario Salmona, Martino Introna, Alberto Mantovani

Research output: Contribution to journalArticlepeer-review


Three molecular forms of the IL-1 receptor antagonist (IL-1ra) have been identified and cloned. Secreted IL-1ra (sIL-1ra or IL-1ra1) contains a classical leader peptide giving a released mature protein. Two intracellular isoforms, icIL-1ra type I (IL-1ra2) and icIL-1ra type II (IL-1ra3), have no leader sequence, thus predicting that these proteins remain intracellular. In an effort to define its biological role, we structurally and functionally characterized IL-1ra3. Endogenous immunoreactive IL-1ra3 was detected in a variety of inflammatory cells and tissues. We used a gene transfer strategy to explore the possible intracellular functions of IL-1ra3 (and IL-1ra2) and the cell-associated agonist IL-1α. The intracellular IL-1ra3 isoform, as well as IL-1ra2, does not block the action of exogenous and endogenous IL-1 under these conditions. Intact IL-1ra3 was released from the cells killed by NK effecters. The intracellular isoforms may represent a reservoir of IL-1ra, released upon cell death, whose function is to limit the pro-inflammatory action of cell debris.

Original languageEnglish
Pages (from-to)781-788
Number of pages8
JournalEuropean Journal of Immunology
Issue number3
Publication statusPublished - 1999


  • IL-1
  • IL-1 receptor antagonist
  • Inflammation

ASJC Scopus subject areas

  • Immunology


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