AI Article Synopsis

  • A segment upstream from the proIL-1beta gene, between -3134 and -2729 bp, was identified as an enhancer that responds to LPS stimulation.
  • The study focused on the area between -3134 and -2987 bp to assess its impact on the proIL-1beta gene's transcription in LPS-stimulated Raw 264.7 cells, revealing that a region from -3134 to -3059 is crucial for inducing transcription.
  • Detailed assays demonstrated specific protein binding in this region that involved NF-kappaB components, indicating that two particular NF-kappaB sites are essential for activating the transcription of the proIL-1beta gene in response to LPS.

Article Abstract

A region between-3134 and -2729 bp upstream from the transcription site of the human pro-interleukin 1beta (proIL-1beta) gene was identified as an LPS-responsive enhancer element. In this study, the influence of the sequences located between -3134 and -2987 on the transcriptional activity of the proIL-1beta gene in LPS-stimulated Raw 264.7 cells was examined in detail. The results obtained by transient transfection of fos -CAT constructs that contained serial 5'-deletion mutations showed that the region between -3134 and -3059 appears to be required for the induction of transcription by LPS. Gel shift assay studies with synthetic oligonucleotides corresponding to partial sequences of the latter region and nuclear extracts from stimulated cells revealed specific protein binding sites between -3110 and -3090 and between -3079 and -3059. These specific bindings were time and LPS dose dependent. The results of supershift analysis using specific antibodies against transcription factors suggested that both binding complexes contained the NF-kappaB components p50 and p65, and did not contain other NF-kappaB proteins (p52, c-Rel, Rel B), AP-1 proteins (c-Fos, C-Jun), CREB or C/EBPbeta (NF-IL6). Mutation of either of the putative NF-kappaB-binding sites in the enhancer element decreased the LPS-stimulated transcriptional activity. These data indicated that two NF-kappaB-binding sites, which are located between -3134 and -3059, are critical for the activation of proIL-1beta gene transcription.

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http://dx.doi.org/10.1006/cyto.1998.0390DOI Listing

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