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

Abstract:

: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.

journal_name

Eur J Immunol

authors

Muzio M,Polentarutti N,Facchetti F,Peri G,Doni A,Sironi M,Transidico P,Salmona M,Introna M,Mantovani A

doi

10.1002/(SICI)1521-4141(199903)29:03<781::AID-IMMU

keywords:

subject

Has Abstract

pub_date

1999-03-01 00:00:00

pages

781-8

issue

3

eissn

0014-2980

issn

1521-4141

journal_volume

29

pub_type

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