Involvement of heat shock protein (Hsp)90β but not Hsp90α 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) 90 beta but not Hsp90 alpha and prevented apoptosis induced by serum starvation or staurosporine treatment. The CpG-B ODN-induced Hsp90 beta expression depended on TLR9, MyD88, and PI3K. Inhibition of Hsp90 beta level by expressing small-interfering RNA suppressed not only Hsp90 beta 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, Hsp90 beta but not Hsp90a was associated with Bcl-2. Inhibition of Hsp90 beta suppressed the CpG-B ODN-induced association of Hsp90 beta 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 Hsp90 beta but not Hsp90 alpha in CpG-B ODN-mediated antiapoptotic response and that Hsp90 beta is distinct from Hsp90 alpha in regulation of the cellular function of immune cells. The Journal of Immunology, 2007, 178: 6100-6108.