TRAIL is involved in CpG ODN-mediated anti-apoptotic signals

Lim,Eun-Jung; Park,Dae-Weon; Jeong,Tae-Whal; Chin,Byung-Rho; Bae,Yoe-Sik; Baek,Suk-Hwan

doi:10.3892/or.2011.1579

TRAIL is involved in CpG ODN-mediated anti-apoptotic signals

Authors:
- Eun-Jung Lim
- Dae-Weon Park
- Tae-Whal Jeong
- Byung-Rho Chin
- Yoe-Sik Bae
- Suk-Hwan Baek
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Affiliations: Department of Biochemistry and Molecular Biology, Aging-Associated Vascular Disease Research Center, College of Medicine, Yeungnam University, Daegu, Republic of Korea, Department of Biochemistry and Molecular Biology, Aging-Associated Vascular Disease Research Center, 210 Main Building, College of Medicine, Yeungnam University, 317-1 Daemyung-5 Dong, Namgu, Daegu 705-802, Republic of Korea
Published online on: December 6, 2011 https://doi.org/10.3892/or.2011.1579
Pages: 1213-1218

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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.

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