cDNA cloning of an intracellular form of the human interleukin 1 receptor antagonist associated with epithelium.
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.
Haskill
S
S
Department of Obstetrics and Gynecology, University of North Carolina, Chapel Hill 27599.
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
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002522:Chlorocebus aethiops; D003001:Cloning, Molecular; D003593:Cytoplasm / Q000502:physiology; D004247:DNA / Q000235:genetics; D004848:Epithelium / Q000502:physiology; D015870:Gene Expression; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000037:antagonists & inhibitors*; D015603:Keratinocytes / Q000502:physiology; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011506:Proteins / Q000235:genetics*; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000235:genetics; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors*; D017472:Receptors, Interleukin-1; D012795:Sialoglycoproteins; D014162:Transfection
C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D011506:Proteins; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D017472:Receptors, Interleukin-1; D012795:Sialoglycoproteins; D004247:DNA