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CDNA cloning of an intracellular form of the human interleukin 1 receptor antagonist associated with epithelium.

ABSTRACT: 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.

SUBMITTER: Haskill S 

PROVIDER: S-EPMC51516 | biostudies-other | 1991 May

REPOSITORIES: biostudies-other

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cDNA cloning of an intracellular form of the human interleukin 1 receptor antagonist associated with epithelium.

Haskill S S   Martin G G   Van Le L L   Morris J J   Peace A A   Bigler C F CF   Jaffe G J GJ   Hammerberg C C   Sporn S A SA   Fong S S  

Proceedings of the National Academy of Sciences of the United States of America 19910501 9

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 sa  ...[more]