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- IFN-γ up-regulates IL-18 gene expression via IFN consensus sequence-binding protein and activator protein-1 elements in macrophages
- Yong Man Kim; Joo Young Im; Seung Hyun Han; Hyung Sik Kang; Inpyo Choi
- Bibliographic Citation
- Journal of Immunology, vol. 165, no. 6, pp. 3198-3205
- Publication Year
- 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.
- Amer Assoc Immunologists
- Appears in Collections:
- Division of Biomedical Research > Personalized Genomic Medicine Research Center > 1. Journal Articles
Division of Biomedical Research > Immunotherapy Research Center > 1. Journal Articles
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