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

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

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: English
• Weight: 168 KB
• Volume: 29
• Category: Article
• ISSN: 0014-2980
• DOI: 10.1002/(sici)1521-4141(199903)29:03<781::aid-immu781>3.0.co;2-0

✦ Synopsis

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-1alpha. 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 effectors. 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.