title: CpG-B oligodeoxynucleotide promotes cell survival via up-regulation of Hsp70 to increase Bcl-xL and to decrease apoptosis-inducing factor translocation.
abstract: Unmethylated CpG oligodeoxynucleotides (ODNs) activate immune responses in a TLR9-dependent manner. In this study, stimulation of mouse macrophages with CpG-B ODN increased cellular Hsp70 expression and prevented apoptosis induced by serum starvation or staurosporine treatment. CpG-B ODN-induced Hsp70 expression depended on TLR9, MyD88, and phosphatidylinositol 3-kinase. Inhibition of Hsp70 synthesis by an inhibitor (quercetin) or antisense hsp70 attenuated not only Hsp70 expression but also the anti-apoptotic capacity of CpG-B ODN. Ectopic expression of Hsp70 rescued the inhibitory effect of quercetin on CpG-B ODN-induced anti-apoptosis. Additional experiments demonstrated that quercetin and anti-sense hsp70 modulated CpG-B ODN-induced anti-apoptosis via a caspase-3-independent pathway by down-regulating the survival gene bcl-x(L) and by increasing translocation of apoptosis-inducing factor. These findings suggest that CpG-B ODN may up-regulate Hsp70 via a TLR9/MyD88/phosphatidylinositol 3-kinase pathway to increase Bcl-x(L) and to decrease apoptosis-inducing factor nuclear translocation, resulting in anti-apoptosis.
authors.affiliation: Agricultural Biotechnology Research Center, Academia Sinica, 128 Academia Road Section 2, Taipei 115, Taiwan.
authors.forename: Cheng-Chin
authors.initials: CC
authors.lastname: Kuo
authors.forename: Shu-Mei
authors.initials: SM
authors.lastname: Liang
authors.forename: Chi-Ming
authors.initials: CM
authors.lastname: Liang
mesh_terms: D000818:Animals; D051033:Apoptosis Inducing Factor / Q000378:metabolism*; D001483:Base Sequence; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000502:physiology*; D018899:CpG Islands / Q000235:genetics*; D017931:DNA Primers; D018840:HSP70 Heat-Shock Proteins / Q000502:physiology*; D006801:Humans; D051379:Mice; D021381:Protein Transport; D015854:Up-Regulation; D051020:bcl-X Protein / Q000378:metabolism*
chemical_list: D051033:Apoptosis Inducing Factor; D017931:DNA Primers; D018840:HSP70 Heat-Shock Proteins; D051020:bcl-X Protein; D053148:Caspase 3