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Title 

IFN-γ up-regulates IL-18 gene expression via IFN consensus sequence-binding protein and activator protein-1 elements in macrophages

Authors 

Yong Man KimJoo Young ImSeung Hyun HanHyung Sik KangInpyo Choi

Publisher 

American Association of Immunologists

Issue Date 

2000

Citation 

Journal of Immunology, vol. 165, no. 6, pp. 3198-3205

Keywords 

interferon consensus sequence binding proteininterferon regulatory factor 1interleukin 18protein antibodytranscription factor AP 1binding siteDNA bindinggene activationgene expression

Abstract 

Constitutive IL-18 expression is detected from many different cells, including macrophages, keratinocytes, and osteoblasts. It has been known that IL-18 gene expression is regulated by two different promoters (p1 promoter and p2 promoter). When RAW 264.7 macrophages were treated with IFN-γ, IL-18 gene expression was increased in a dose- and time-dependent manner. IFN-γ activated the inducible promoter 1, but not the constitutive promoter 2. Mutagenesis studies indicated that an IFN consensus sequence-binding protein (ICSBP) binding site between -39 and -22 was critical for the IFN-γ inducibility. EMSA using an ICSBP oligonucleotide probe showed that IFN-γ treatment increased the formation of DNA-binding complex, which was supershifted with anti-IFN regulatory factor-1 Ab and anti-ICSBP Ab. Another element, an AP-1 site between -1120 and -1083, was important. EMSA using an AP-1-specific oligonucleotide demonstrated that IFN-γ or LPS treatment increased the AP-1-binding activity. The addition of anti-c-Jun Ab or anti-c-Fos Ab to IFN-γ- or LPS-treated nuclear extracts resulted in the reduction of AP-1 complex or the formation of a supershifted complex. Taken together, these results indicate that IFN-γ increased IL-18 gene expression via ICSBP and AP-1 elements.

ISSN 

0022-1767

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2017-04-19


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