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IRF-1-mediated IFN-γ enhancement of TRAIL-induced apoptosis  

Park, Sang-Youel (Bio-Safty Research Institute, Chonbuk National University)
Seol, Jae-Won (College of Veterinary Medicine, Chonbuk National University)
Lee, You-Jin (College of Veterinary Medicine, Chonbuk National University)
Kang, Seog-Jin (National Livestock Research Institute)
Kim, In-shik (Bio-Safty Research Institute, Chonbuk National University)
Kang, Hyung-sub (Bio-Safty Research Institute, Chonbuk National University)
Chae, Joon-seok (Bio-Safty Research Institute, Chonbuk National University)
Cho, Jong-Hoo (Bio-Safty Research Institute, Chonbuk National University)
Publication Information
Korean Journal of Veterinary Research / v.44, no.2, 2004 , pp. 195-200 More about this Journal
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.
Keywords
IFN-${\gamma}$; TRAIL; IRF-1; HeLa;
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