Transcriptional regulation of interleukin-1β gene by interleukin-1β itself is mediated in part by Oct-1 in thymic stromal cells

Abstract

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-1β increased steady- state mRNA levels for IL-1α and IL-1β in TSC-936 and TSC-2C4 cells; stability was not a major determinant of this effect. To study transcriptional regulation of IL-1β, we functionally characterized 4 kilobase pairs of the 5'-flanking region and first intron of the bovine IL- 1β gene. The -470/+14 fragment was sufficient to confer maximal responsiveness to IL-1β upon transfection into these cell lines. Progressive 5' deletions identified several IL-1β-responsive regions, including -308 to -226, which we further characterized. Electrophoretic mobility shift and supershift analyses showed that IL-1β 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-1β transcription by IL-1β itself.