title: TRAIL is involved in CpG ODN-mediated anti-apoptotic signals.
abstract: Synthetic oligodeoxynucleotides (ODNs) with the CpG-motifs are recognized             by toll-like receptor 9 (TLR9), which elicits an immune response. Serum starvation             of Raw264.7 cells increased tumor necrosis factor-related apoptosis-inducing ligand             (TRAIL) expression. However, treatment with CpG ODN reduced TRAIL expression as             well as apoptosis by serum starvation. In serum starved cells, TLR9 inhibitors             recovered the decreasing TRAIL expression and sub-G1 accumulation by CpG ODN.             CpG ODN-regulated anti-apoptotic signals which were dependent on the Akt-FoxO3a             signaling pathway. CpG ODNs activated Akt and inactivated FoxO3a in serum starved             cells. Knockdown of FoxO3a by siRNA decreased TRAIL expression and apoptosis in             serum-starved cells. In contrast, FoxO3a overexpression increased apoptosis by             serum starvation, and CpG ODNs blocked these effects through TRAIL expression.             LY294002, a PI3K-Akt inhibitor, blocked the CpG ODN effect of TRAIL expression             and the sub-G1 population in serum starved cells. In contrast, overexpression             of wild-type Akt reduced additional sub-G1 cells both in non-CpG ODN- and CpG             ODN-treated cells. Taken together, these results demonstrate the involvement of             Akt-FoxO3a signaling in TLR9-mediated downregulation of TRAIL and anti-apoptotic             signals.
authors.affiliation: Department of Biochemistry and Molecular Biology, Aging-Associated                     Vascular Disease Research Center, College of Medicine, Yeungnam University,                     Daegu, Republic of Korea.
authors.forename: Eun-Jung
authors.initials: EJ
authors.lastname: Lim
authors.forename: Dae-Weon
authors.initials: DW
authors.lastname: Park
authors.forename: Tae-Whal
authors.initials: TW
authors.lastname: Jeong
authors.forename: Byung-Rho
authors.initials: BR
authors.lastname: Chin
authors.forename: Yoe-Sik
authors.initials: YS
authors.lastname: Bae
authors.forename: Suk-Hwan
authors.initials: SH
authors.lastname: Baek
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D016895:Culture Media, Serum-Free; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D009838:Oligodeoxyribonucleotides / Q000378:metabolism*; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D015398:Signal Transduction / Q000187:drug effects; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism*; D013997:Time Factors; D051217:Toll-Like Receptor 9 / Q000187:drug effects / Q000378:metabolism; D014162:Transfection
chemical_list: C408982:CPG-oligonucleotide; D016895:Culture Media, Serum-Free; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; C474033:FoxO3 protein, mouse; D009838:Oligodeoxyribonucleotides; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D053221:TNF-Related Apoptosis-Inducing Ligand; C495370:Tlr9 protein, mouse; C505654:Tnfsf10 protein, mouse; D051217:Toll-Like Receptor 9; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt