Synergistic transcriptional activation of the IL-8 gene by NF-kappa B p65 (RelA) and NF-IL-6.

Transcriptional activation of the IL-8 gene by several inflammatory mediators, including the cytokines IL-1 and TNF-alpha, is mediated through sequences located between nucleotide -94 and -71 of the IL-8 promoter. Because adjacent binding sites for the inducible transcription factors NF-kappa B and NF-IL-6 are located within this region, we examined the functional interaction of these two transcription factor families in IL-8 gene regulation. Maximal transcriptional activation by PMA in Jurkat T lymphocytes was shown to require intact binding sites for both NF-kappa B and NF-IL-6. Electrophoretic mobility shift analysis indicates that NF-IL-6, as well as other related members of this family, bind specifically to the NF-IL-6 site in the IL-8 promoter. In addition, NF-kappa B p65 (RelA), but not NF-kappa B p50 (NFKB1), binds specifically to the NF-kappa B site. When incubated together, RelA and NF-IL-6/C/EBP form a ternary complex with this region of the IL-8 promoter; this binding is dependent on intact binding sites for both NF-IL-6 and RelA. Transient cotransfection analyses indicate that the cooperative association of NF-IL-6 and RelA with the IL-8 promoter results in synergistic transcriptional activation. Mutational analyses of RelA demonstrate that the C-terminal transactivation domain and the DNA binding domain are required for synergistic activation with NF-IL-6. In addition, overexpression of the NF-kappa B inhibitor molecule, I kappa B, abolished the RelA- and RelA/NF-IL-6-dependent synergistic activation. These data demonstrate that RelA and members of the C/EBP/NF-IL-6 family can functionally cooperate in transcriptional activation of the IL-8 gene and suggest a common mechanism for inducible regulation of cytokine gene expression.

Kunsch C ，Lang RK ，Rosen CA ，Shannon MF ... -  《JOURNAL OF IMMUNOLOGY》

Cooperative binding and synergistic activation by RelA and C/EBPbeta on the intercellular adhesion molecule-1 promoter.

Catron KM ，Brickwood JR ，Shang C ，Li Y ，Shannon MF ，Parks TP ... -  《-》

Cytokine induction of monocyte chemoattractant protein-1 gene expression in human endothelial cells depends on the cooperative action of NF-kappa B and AP-1.

Martin T ，Cardarelli PM ，Parry GC ，Felts KA ，Cobb RR ... -  《EUROPEAN JOURNAL OF IMMUNOLOGY》

Activation of IL-2 receptor alpha-chain gene by individual members of the rel oncogene family in association with serum response factor.

Pierce JW ，Jamieson CA ，Ross JL ，Sen R ... -  《JOURNAL OF IMMUNOLOGY》

[Synergism between transcription factors NF-IL6 and NF-kappa B in IL-6 gene regulation].

Fujikawa K 《-》