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

TRAIL 유도 세포사멸에 있어서 IFN-γ의한 증가 기전 연구: IRF-1과의 관련성

  • 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)
  • 박상열 (전북대학교 생체안정성연구소) ;
  • 설재원 (전북대학교 수의과대학) ;
  • 이유진 (전북대학교 수의과대학) ;
  • 강석진 (축산기술연구소) ;
  • 김인식 (전북대학교 생체안정성연구소) ;
  • 강형섭 (전북대학교 생체안정성연구소) ;
  • 채준석 (전북대학교 생체안정성연구소) ;
  • 조종후 (전북대학교 생체안정성연구소)
  • Accepted : 2004.04.17
  • Published : 2004.06.30

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.

Acknowledgement

Supported by : 전북대학교

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