First Author | Kuo CC | Year | 2007 |
Journal | J Immunol | Volume | 178 |
Issue | 10 | Pages | 6100-8 |
PubMed ID | 17475835 | Mgi Jnum | J:146128 |
Mgi Id | MGI:3836717 | Doi | 10.4049/jimmunol.178.10.6100 |
Citation | Kuo CC, et al. (2007) Involvement of heat shock protein (Hsp)90 beta but not Hsp90 alpha in antiapoptotic effect of CpG-B oligodeoxynucleotide. J Immunol 178(10):6100-8 |
abstractText | 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. |