An essential role for NF-κB in IL-18-induced IFN-γ expression in KG-1 cells

H Kojima, Y Aizawa, Y Yanai, K Nagaoka… - The Journal of …, 1999 - journals.aai.org
H Kojima, Y Aizawa, Y Yanai, K Nagaoka, M Takeuchi, T Ohta, H Ikegami, M Ikeda…
The Journal of Immunology, 1999journals.aai.org
IL-18 is a multifunctional cytokine playing various regulatory roles in the immune system
including induced cytokine production. As a part of our ongoing studies on the molecular
mechanisms of IL-18-induced IFN-γ production, we have examined the transcriptional
regulation of the IFN-γ gene by IL-18 in a human myelomonocytic cell line, KG-1. On the
basis of DNA/protein binding, we have determined an IL-18-inducible NF-κB binding site
located at− 786 to− 776 of the IFN-γ gene regulatory region (designated KBBsite). Transient …
Abstract
IL-18 is a multifunctional cytokine playing various regulatory roles in the immune system including induced cytokine production. As a part of our ongoing studies on the molecular mechanisms of IL-18-induced IFN-γ production, we have examined the transcriptional regulation of the IFN-γ gene by IL-18 in a human myelomonocytic cell line, KG-1. On the basis of DNA/protein binding, we have determined an IL-18-inducible NF-κB binding site located at− 786 to− 776 of the IFN-γ gene regulatory region (designated KBBsite). Transient transfection of promoter-reporter gene constructs revealed that the KBBsite is required for full IL-18-induced activation of the IFN-γ gene transcription induced by IL-18. In addition, stable transformants of a dominant-negative form of the IκBα showed an inhibition of IL-18-dependent IκBα degradation, NF-κB activation, and expression of IFN-γ. These results are the first to show the actual significance of the NF-κB pathway in the regulation of IFN-γ gene expression by IL-18.
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