TAILIEUCHUNG - Báo cáo khoa học: IFN-c enhances TRAIL-induced apoptosis through IRF-1

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is amember of theTNFfamilyandapotent inducer of apoptosis. TRAIL has been shown to effectively limit tumor growthin vivowithout detectable cytotoxic side-effects. Interferon (IFN)-coften modulates the anticancer activities of TNF family members including TRAIL. How-ever, little is known about the mechanism. To explore the mechanism, A549, HeLa, LNCaP, Hep3B andHepG2 cells were pretreated with IFN-c, and then exposed to TRAIL. | Eur. J. Biochem. 271 4222-4228 2004 FEBS 2004 doi IFN-c enhances TRAIL-induced apoptosis through IRF-1 Sana-Youel Park1 Jae-Won Seol1. You-Jin Lee1. Jona-Hoo Cho1. Hvuna-Sub Kana1. In-Shik Kim1 Soo-Hyun Park1 Tae-Hyoung Kim2 John H. Yim3 Moonil Kim3 Timothy R. Billiar3 and Dai-Wu Seol3 1 Bio-Safety Research Institute College of Veterinary Medicine Chonbuk National University Jeonju Jeonbuk South Korea department of Biochemistry Chosun University School of Medicine Dong-Gu Gwangju South Korea 3Department of Surgery University of Pittsburgh School of Medicine Pittsburgh PA USA Tumor necrosis factor TNF -related apoptosis-inducing ligand TRAIL is a member of the TNF family and a potent inducer of apoptosis. TRAIL has been shown to effectively limit tumor growth in vivo without detectable cytotoxic sideeffects. Interferon IFN -y often modulates the anticancer activities of TNF family members including TRAIL. However little is known about the mechanism. To explore the mechanism A549 HeLa LNCaP Hep3B and HepG2 cells were pretreated with IFN-y and then exposed to TRAIL. IFN-y pretreatment augmented TRAIL-induced apoptosis in all these cell lines. A549 cells were selected and further characterized for IFN-y action in TRAIL-induced apoptosis. Western blotting analyses revealed that IFN-y dramatically increased the protein levels of interferon regulatory factor IRF -1 but not TRAIL receptors DR4 and DR5 and pro-apoptotic FADD and Bax and anti-apoptotic factors Bcl-2 Bcl-XL cIAP-1 cIAP-2 and XIAP .To elucidate the functional role of IRF-1 in IFN-y-enhanced TRAIL-induced apoptosis IRF-1 was first overexpressed by using an adenoviral vector AdIRF-1. IRF-1 overexpression minimally increased apoptotic cell death but significantly enhanced apoptotic cell death induced by TRAIL when infected cells were treated with TRAIL. In further experiments using an antisense oligonucleotide a specific repression of IRF-1 expression abolished enhancer activity .

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