Acute-phase reaction induces a specific complex between hepatic nuclear proteins and the interleukin 6 response element of the rat alpha 2-macroglobulin gene.
Interleukin 6 (IL-6) was established as a transcriptional inducer of the rat alpha 2-macroglobulin gene, a prototype liver acute-phase gene. Maximum induction occurred when the 5' flanking sequences of this gene (position -209 to -43) directed expression from the gene's own TATA box and transcription start site. Removal of the hexanucleotide CTGGGA (position -164 to -159) abolished 60-70% of the hormonal induction in FAO1 rat hepatoma cells. This hexanucleotide was defined as the IL-6 response element (IL-6-RE). The IL-6-RE is well conserved in the cytokine-responsive regions of other acute-phase genes and serves as a binding site for nuclear proteins. A characteristic DNA-protein complex (complex I) was formed with nuclear proteins from normal rat livers. A different, hormone-inducible complex (complex II) was assembled specifically with nuclear proteins from acute-phase rat livers or from IL-6-treated human Hep 3B hepatoma cells. Complex II was competitively inhibited by oligonucleotides representing the conserved IL-6-RE sequence from other acute-phase genes. Thus, the proteins building complex II likely participate in a general signal transduction mechanism mediating the transcriptional activation by IL-6 of several acute-phase genes.
Department of Immunology, Research Institute of Scripps Clinic, La Jolla, CA 92037.
M
M
Hattori
L J
LJ
Abraham
W
W
Northemann
G H
GH
Fey
D000818:Animals; D001483:Base Sequence; D004247:DNA / Q000187:drug effects / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D003850:Deoxyribonuclease I; D003907:Dexamethasone / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D005796:Genes / Q000187:drug effects; D015850:Interleukin-6 / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism*; D008114:Liver Neoplasms, Experimental / Q000378:metabolism*; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism*; D009710:Nucleotide Mapping; D011401:Promoter Regions, Genetic; D051381:Rats; D014162:Transfection; D000511:alpha-Macroglobulins / Q000235:genetics*
D004268:DNA-Binding Proteins; D015850:Interleukin-6; D009687:Nuclear Proteins; D000511:alpha-Macroglobulins; D003907:Dexamethasone; D004247:DNA; D003850:Deoxyribonuclease I