Transcriptional regulation of interleukin-1beta gene by interleukin-1beta itself is mediated in part by Oct-1 in thymic stromal cells.
Interleukin (IL)-1 is involved in many processes, including thymic development. However, control of IL-1 expression in thymic-derived stromal cells (TSC) has not been reported. We found that IL-1beta increased steady-state mRNA levels for IL-1alpha and IL-1beta in TSC-936 and TSC-2C4 cells; stability was not a major determinant of this effect. To study transcriptional regulation of IL-1beta, we functionally characterized 4 kilobase pairs of the 5'-flanking region and first intron of the bovine IL-1beta gene. The -470/+14 fragment was sufficient to confer maximal responsiveness to IL-1beta upon transfection into these cell lines. Progressive 5' deletions identified several IL-1beta-responsive regions, including -308 to -226, which we further characterized. Electrophoretic mobility shift and supershift analyses showed that IL-1beta induced the ability to form multiple protein complexes with -261/-226 and that one of these contained nuclear factor Oct-1. A competitor containing a mutated Oct consensus site failed to compete not only for this complex but others as well, suggesting that this sequence regulates binding of other proteins to this region. Functional analysis confirmed that this element was essential for maximal induction of transcription. These findings document a heretofore undescribed mechanism utilized by TSC for regulation of IL-1beta transcription by IL-1beta itself.
Tseng
Y H
YH
Program of Developmental Biology, Department of Comparative Biosciences, University of Wisconsin, Madison, Wisconsin 53706, USA.
Schuler
L A
LA
D000818:Animals; D001483:Base Sequence; D002417:Cattle; D003001:Cloning, Molecular; D004247:DNA; D004268:DNA-Binding Proteins; D005786:Gene Expression Regulation / Q000502:physiology*; D018398:Homeodomain Proteins / Q000378:metabolism*; D051863:Host Cell Factor C1; D007375:Interleukin-1 / Q000235:genetics* / Q000502:physiology; D008969:Molecular Sequence Data; D050811:Octamer Transcription Factor-1; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics; D012689:Sequence Homology, Nucleic Acid; D015398:Signal Transduction; D017154:Stromal Cells / Q000378:metabolism*; D013950:Thymus Gland / Q000166:cytology / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D051863:Host Cell Factor C1; D007375:Interleukin-1; D050811:Octamer Transcription Factor-1; D012333:RNA, Messenger; D014157:Transcription Factors; D004247:DNA