Involvement of a NF-kappa B-like transcription factor in the activation of the interleukin-6 gene by inflammatory lymphokines.

Abstract

Interleukin-6 (IL-6) is one of the major mediators of inflammation, and its expression is inducible by the other inflammatory lymphokines, interleukin-1 (IL-1) and tumor necrosis factor a (TNF-a). We demonstrate that a common IL-6 promoter element, termed inflammatory lymphokine-responsive element (ILRE), is important for induction of IL-6 gene expression by IL-1 and TNF-a despite possible differences in the mechanisms of action of these lymphokines. Remarkably, the ILRE sequence, located between -73 to -63 relative to the mRNA cap site, is highly homologous to NF-KB transcription factor-binding motifs and binds an IL-1-TNF-a-inducible nuclear factor; the sequence specificities, binding characteristics, and subcellular vocalizations of this factor are indistinguishable from those of NF-KB. In addition, mutations of the ILRE sequence which impair the binding of this nuclear factor abolished the induction of IL-6 gene expression by IL-1 and TNF-a in vivo. These results indicate that a nuclear factor indistinguishable from NF-KB is involved in the transcriptional activation of the IL-6 gene by IL-1 and TNF-a.

Transcriptional regulatory effects of lymphoma-associated NFKB2/lyt10 protooncogenes

“…The pIL6-kB-CAT reporter plasmid contains three copies of the kB motif derived from the IL-6 promoter (Shimizu et al, 1990) directing expression of the CAT gene from the original IL-6 basal promoter. The pIL6-kB-CAT plasmid exhibited very high basal activity in COS7 cells (data not shown).…”

Atiprimod blocks STAT3 phosphorylation and induces apoptosis in multiple myeloma cells

“…Since IL-6 expression is regulated by NF-kB (Shimizu et al, 1990), we investigated whether Atiprimod inhibits NF-kB activity. The NF-kB transcription factor family is an important modulator of cellular proliferation, suppression of apoptosis, enhancement of tumour cell invasiveness, and induction of angiogenesis (Orlowski and Baldwin, 2002).…”

“…Since the expression of IL-6 is regulated by NF-kB (Shimizu et al, 1990) and Atiprimod downregulates IL-6 production, we hypothesised that Atiprimod inhibits NF-kB. To test this hypothesis, we used U266-B1 cells, which constitutively express active NF-kB (Ni et al, 2001;Bharti et al, 2004) and produce IL-6 (Catlett-Falcone et al, 1999;Bharti et al, 2003).…”

Effects of tacrolimus on ischemia-reperfusion injury

“…This ubiquitous transcription factor mediates early gene expression of cytokines, chemokines, growth factors, immunoreceptors, and cell adhesion molecules during I-R injury. 65,[74][75][76][77][78][79][80][81][82][83][84] Selective blockade of NF-B with proline dithiocarbamate during the early phase of reperfusion resulted in remarkable tissue protection after severe ischemic stress. 85 In parallel, tacrolimus has been documented to block early activation of NF-B.…”