Involvement of Heat Shock Protein (Hsp)90β but Not Hsp90α in Antiapoptotic Effect of CpG-B Oligodeoxynucleotide

Abstract

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) 90β but not Hsp90α and prevented apoptosis induced by serum starvation or staurosporine treatment. The CpG-B ODN-induced Hsp90β expression depended on TLR9, MyD88, and PI3K. Inhibition of Hsp90β level by expressing small-interfering RNA suppressed not only Hsp90β 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, Hsp90β but not Hsp90α was associated with Bcl-2. Inhibition of Hsp90β suppressed the CpG-B ODN-induced association of Hsp90β 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 Hsp90β but not Hsp90α in CpG-B ODN-mediated antiapoptotic response and that Hsp90β is distinct from Hsp90α in regulation of the cellular function of immune cells.