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CpG-B oligodeoxynucleotide promotes cell survival via up-regulation of Hsp70 to increase Bcl-xL and to decrease
Cheng-Chin Kuo1, Shu-Mei Liang, Chi-Ming Liang
1Agricultural Biotechnology Research Center, Academia Sinica, 128 Academia Road Section 2, Taipei 115, Taiwan.
The Journal of Biological Chemistry
|October 19, 2006
Summary
CpG-B oligodeoxynucleotides (ODNs) boost immune cells by increasing heat shock protein 70 (Hsp70) expression. This Hsp70 upregulation, dependent on TLR9 signaling, protects macrophages from cell death.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Unmethylated CpG oligodeoxynucleotides (ODNs) are known immune stimulants via Toll-like receptor 9 (TLR9).
- Heat shock protein 70 (Hsp70) plays a critical role in cellular protection and stress response.
Purpose of the Study:
- To investigate the role of Hsp70 in CpG-B ODN-mediated immune responses.
- To elucidate the signaling pathway involved in CpG-B ODN-induced Hsp70 expression and anti-apoptosis.
Main Methods:
- Stimulation of mouse macrophages with CpG-B ODN.
- Assessment of Hsp70 expression and apoptosis.
- Inhibition of Hsp70 synthesis using quercetin or antisense hsp70.
- Analysis of signaling pathways including TLR9, MyD88, and phosphatidylinositol 3-kinase.
- Evaluation of caspase-3 activity and apoptosis-inducing factor translocation.
Main Results:
- CpG-B ODN treatment increased Hsp70 expression and conferred resistance to apoptosis in macrophages.
- This effect was dependent on TLR9, MyD88, and phosphatidylinositol 3-kinase signaling.
- Inhibition of Hsp70 attenuated the anti-apoptotic effects of CpG-B ODN.
- CpG-B ODN-induced anti-apoptosis involved a caspase-3-independent pathway, down-regulation of Bcl-x(L), and reduced translocation of apoptosis-inducing factor.
Conclusions:
- CpG-B ODN upregulates Hsp70 via the TLR9/MyD88/PI3K pathway.
- Hsp70 contributes to the anti-apoptotic effects of CpG-B ODN by modulating Bcl-x(L) and apoptosis-inducing factor.
- CpG-B ODN exhibits cytoprotective properties through Hsp70 induction.
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