Constitutive and interleukin-1 (IL-1)-inducible factors interact with the IL-1-responsive element in the IL-6 gene.

Abstract

The interleukin-6 (IL-6) promoter is rapidly and transiently activated with other cytokines, including IL-1, tumor necrosis factor, and platelet-derived growth factor, as well as phorbol esters and agents that increase intracellular cyclic AMP. In this study, we have investigated cis-acting regulatory elements and trans-acting factors responsible for IL-i-induced IL-6 gene expression. Studies on the 5' deletion mutants of the human IL-6 gene suggested that the IL-i-responsive element was mapped within the IL-6 promoter region (-180 to -123) which was homologous to the c-fos serum-responsive enhancer element. Gel retardation assay identified two types of nuclear factors that bound to this region, one constitutive and the other inducible. These two factors recognized a 14-base-pair (bp) palindromic sequence, ACATTGCACAATCT. Furthermore, three copies of this 14-bp palindrome conferred IL-1 responsiveness to the basal enhancerless IL-6 promoter, indicating that a 14-bp-dyad symmetry sequence was an IL-i-responsive element in the IL-6 gene.

Genistein induces adipogenesis but inhibits leptin induction in human synovial fibroblasts

“…Rosiglitazone, when applied at high concentrations (50 mM), had a significant but an inferior inhibitory effect on TNF-a-induced IL-6 production compared with genistein, which also inhibited both endogenous and TNF-a-induced C/EBP-b, a transcription factor involved in inflammation 23 and adipocyte differentiation, 24 as well as p65 unit of NF-kB. Promoters of IL-6 and IL-8 have binding sites for both C/ EBP-b and NF-kB, 18,19 and functional and physical associations between NF-kB and C/EBP have been shown. 25 The inhibitory effect of genistein on NF-kB-mediated transcription of IL-6 has been shown 20 and we have presented, in this study, that genistein inhibits the binding of C/EBP-b on the IL-8 promoter.…”

“…Genistein Inhibits Endogenous and TNF-a-Induced p38, C/EBP and NF-jB Pathways As both genistein and p38 inhibitor, SB203580, inhibited endogenous and TNF-a-induced synovial fibroblasts IL-6 and IL-8 production (Figure 2c and d), and because promoters of IL-6 and IL-8 have binding sites for both C/EBP-b and NF-kB, 18,19 we have tested the effect of TNF-a and PPAR-g agonists on the expression of these proteins in synovial fibroblasts. Western blots showed that TNF-a induced phosphorylation of p38, and expression of p38, C/EBP-b and p65 unit of NF-kB ( Figure 3).…”

Aberrant proteolysis of the β‐amyloid precursor protein in familial Alzheimer's disease lymphoblastoid cells

“…2B) than normal cells. Goldgaber et al [28] reported that IL-1 stimulation of APP occurs via proteinkinase-C-mediated upregulation of the upstream AP-l-binding site at the -350 nuclcotidc position of the APP promoter [12] because the promotor does not have the consensus IL-1 responsive element [31]. Furthermore, there are the important findings of increases of IL-1 and APP in microglia and reactive astrocytcs in Alzheimer's disease and Down's-syndrome brains [27].…”

Augmentation of haptoglobin production in Hep3B cell line by a nuclear factor NF‐IL6

“…Our previous report [6] showed that IL-l-dependent transcriptional activation of the IL-6 gene was regulated via a 14.bp palindrome sequence at position -150 bp relative to the cap site, and a novel nuclear factor (NF-IL6) was specifically able to recognize the sequence 161. The molecular cloning of the NF-IL6 gene demonstrated the high homology of its leucine zipper sequence and basic domain with a liver-specific CCA.AT/enhancer binding protein (C/EBP) [7].…”