Involvement of heat shock protein (Hsp)90 beta but not Hsp90 alpha in antiapoptotic effect of CpG-B oligodeoxynucleotide.
Unmethylated CpG oligodeoxynucleotides (CpG ODNs) activate immune responses in a TLR9-dependent manner. In this study, we found that stimulation of mouse macrophages and dendritic cells with B-type CpG ODN (CpG-B ODN) increased the cellular level of heat shock protein (Hsp) 90beta but not Hsp90alpha and prevented apoptosis induced by serum starvation or staurosporine treatment. The CpG-B ODN-induced Hsp90beta expression depended on TLR9, MyD88, and PI3K. Inhibition of Hsp90beta level by expressing small-interfering RNA suppressed not only Hsp90beta expression but also PI3K-dependent phosphorylation of Akt and CpG-B ODN-mediated antiapoptosis. Additional studies demonstrated that as described by other group in mast cells, Hsp90beta but not Hsp90alpha was associated with Bcl-2. Inhibition of Hsp90beta suppressed the CpG-B ODN-induced association of Hsp90beta with Bcl-2 and impaired the inhibitory effect of CpG-B ODN in the release of cytochrome c and activation of caspase-3. This study thus reveals the involvement of Hsp90beta but not Hsp90alpha in CpG-B ODN-mediated antiapoptotic response and that Hsp90beta is distinct from Hsp90alpha in regulation of the cellular function of immune cells.
Kuo
Cheng-Chin
CC
Agricultural Biotechnology Research Center, Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan.
Liang
Chi-Ming
CM
Lai
Chen-Yen
CY
Liang
Shu-Mei
SM
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology*; D002460:Cell Line; D045744:Cell Line, Tumor; D018841:HSP90 Heat-Shock Proteins / Q000096:biosynthesis / Q000502:physiology*; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D053594:Myeloid Differentiation Factor 88 / Q000502:physiology; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D020033:Protein Isoforms / Q000502:physiology*; D015398:Signal Transduction / Q000276:immunology; D051217:Toll-Like Receptor 9 / Q000502:physiology; D015854:Up-Regulation / Q000276:immunology
D000276:Adjuvants, Immunologic; C408982:CPG-oligonucleotide; D018841:HSP90 Heat-Shock Proteins; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D009838:Oligodeoxyribonucleotides; D020033:Protein Isoforms; C495370:Tlr9 protein, mouse; D051217:Toll-Like Receptor 9; D019869:Phosphatidylinositol 3-Kinases