Open AccesscDNA cloning of an intracellular form of the human interleukin 1 receptor antagonist associated with epithelium.
Author(s) -
Stephen Haskill,
George A. Martin,
Linda Van Le,
J. Steven Morris,
Amy A. Peace,
Carl F. Bigler,
G. J. Jaffe,
Craig Hammerberg,
Sarah A. Sporn,
Susan Fong
Publication year - 1991
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.88.9.3681
Subject(s) - intracellular , autocrine signalling , interleukin 12 receptor, beta 1 subunit , interleukin 1 receptor antagonist , complementary dna , biology , microbiology and biotechnology , interleukin 1 receptor, type i , interleukin 1 receptor, type ii , receptor , receptor antagonist , interleukin , gene , antagonist , cytokine , immunology , genetics , interleukin 5
A cDNA encoding a receptor antagonist of interleukin 1 (IL-1ra), secreted from human monocytes, has recently been isolated and sequenced [Eisenberg, S. P., Evans, R. J., Arend, W. P., Verderber, E., Brewer, M. T., Hannum, C. H. & Thompson, R. C. (1990) Nature (London) 343, 341-346]. We have identified another version of this IL-1ra, which is predominantly expressed in epithelial cells. This IL-1ra lacks a leader sequence and, thus, is probably intracellular. Both proteins are derived from the same gene through use of an alternative transcriptional start site and internal splice-acceptor site. Expression of intracellular IL-1ra cDNA in COS cells demonstrated that the intracellular product specifically inhibited exogenous interleukin 1-dependent responses. Keratinocytes were shown to contain significant amounts of nonsecreted IL-1ra protein. Constitutive expression of the intracellular IL-1ra may be an intracellular defensive mechanism in exposed epithelial cells and/or may serve to regulate autocrine interleukin 1-mediated pathways of differentiation.