Korean Journal of Veterinary Research 2004;44(2):195-200.
IRF-1-mediated IFN-γ enhancement of TRAIL-induced apoptosis
Sang-Youel Park1, Jae-Won Seol2, You-Jin Lee2, Seog-Jin Kang3, In-shik Kim1, Hyung-sub Kang1, Joon-seok Chae1, Jong-Hoo Cho1
1Bio-Safty Research Institute, Chonbuk National University
2College of Veterinary Medicine, Chonbuk National University
3National Livestock Research Institute
TRAIL 유도 세포사멸에 있어서 IFN-γ의한 증가 기전 연구: IRF-1과의 관련성
박상열1, 설재원2, 이유진2, 강석진3, 김인식1, 강형섭1, 채준석1, 조종후1
1전북대학교 생체안정성연구소
2전북대학교 수의과대학
3축산기술연구소
Abstract
Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a member of the TNF family and potent inducer of apoptosis. TRAIL has been shown to effectively limit tumor growth in vivo without detectable cytotoxic side effects. Interferon (IFN)-${gamma}$ often modulates the anti-cancer activities of TNF family members including TRAIL. We previously reported that IFN-${gamma}$ enhanced TRAIL-induced Apoptosis in HeLa cells without the unknown mechanism. In this study, we investigated whether IRF-1 involves in IFN-${gamma}$-enhanced TRAIL-induced apoptosis. We exposed HeLa cells to IFN-${gamma}$ for 12 hours and then treated with recombinant TRAIL protein. No apoptosis was induced in cells pretreated with IFN-${gamma}$, and TRAIL only induced 30% apoptosis after 3 hours treatment. In HeLa cells pretreated with IFN-${gamma}$, TRAIL induced cell death to more than 75% at 3 hours, showed that IFN-${gamma}$-pretreatment enhanced HeLa cell death to TRAIL-induced apoptosis. To investigate the functional role of IRF-1 in IFN-${gamma}$-enhanced TRAIL-induced apoptosis, IRF-1 was overexpressed by using an adenoviral vector AdIRF-1. IRF-1 overexpression increased apoptotic cell death and significantly enhanced apoptotic cell death induced by TRAIL when infected cells were treated with TRAIL. Our findings show that IFN-${gamma}$ enhances TRAIL-induced apoptosis by IRF-1 in HeLa cells.
Key Words: IFN-${gamma}$, TRAIL, IRF-1, HeLa
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