title: Regulation of transcription of the intracellular interleukin-1 receptor antagonist gene by AP-1 in mouse carcinoma cells.
abstract: Interleukin-1 receptor antagonist (IL-1Ra) is involved in many processes, including epidermal inflammation and hyperplasia after irritation or injury. However, the mechanism by which intracellular IL-1Ra (icIL-1Ra) expression is regulated in mouse keratinocytes has not been reported. We found that the CH72 mouse carcinoma cell line constitutively expresses the icIL-1Ra mRNA. To study the transcriptional factors responsible for the constitutive expression of icIL-1Ra, we functionally characterized 4.5 kb of the 5' flanking region of the human icIL-1Ra gene in these cells. We first demonstrated that icIL-1Ra expression in these cells was regulated at the level of transcription. Deletion analysis of the promoter showed that regulatory elements for constitutive expression were located -158 to -49 bp upstream of the transcription start site for icIL-1Ra. We investigated the cis- and trans-acting factors required for icIL-1Ra expression. An activating protein-1 (AP-1) site was identified as the positive regulatory element necessary for the constitutive expression of the icIL-1Ra promoter in CH72 cells. Moreover, electrophoretic mobility shift assay and cotransfection experiments showed that c-jun and c-fos proteins bound to the AP-1 site and functionally transactivated the icIL-1Ra promoter in mouse carcinoma CH72 cells.
authors.affiliation: The University of Texas M. D. Anderson Cancer Center, Science Park-Research Division, Smithville, Texas 78957, USA.
authors.forename: Eunhye
authors.initials: E
authors.lastname: La
authors.forename: Joyce E
authors.initials: JE
authors.lastname: Rundhaug
authors.forename: Amy
authors.initials: A
authors.lastname: Pavone
authors.forename: Susan M
authors.initials: SM
authors.lastname: Fischer
mesh_terms: D000818:Animals; D001483:Base Sequence; D002294:Carcinoma, Squamous Cell; D016384:Consensus Sequence; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D017930:Genes, Reporter; D053590:Interleukin 1 Receptor Antagonist Protein; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D011994:Recombinant Proteins / Q000378:metabolism; D016415:Sequence Alignment; D017384:Sequence Deletion; D012795:Sialoglycoproteins / Q000235:genetics*; D012878:Skin Neoplasms; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology*; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: C507763:IL1RN protein, human; C507764:Il1rn protein, mouse; D053590:Interleukin 1 Receptor Antagonist Protein; D011994:Recombinant Proteins; D012795:Sialoglycoproteins; D018808:Transcription Factor AP-1; D008156:Luciferases