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Involvement of Heat Shock Protein (Hsp)90 but Not Hsp90 in Antiapoptotic Effect of CpG-B Oligodeoxynucleotide¹

Cheng-Chin Kuo^*, Chi-Ming Liang^2,,,, Chen-Yen Lai^* and Shu-Mei Liang^2,*,

^* Agricultural Biotechnology Research Center, Genomics Research Center, and Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan; and Division of Molecular and Genomic Medicine, National Health Research Institutes, Miaoli County, Taiwan

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 but not Hsp90 and prevented apoptosis induced by serum starvation or staurosporine treatment. The CpG-B ODN-induced Hsp90 expression depended on TLR9, MyD88, and PI3K. Inhibition of Hsp90 level by expressing small-interfering RNA suppressed not only Hsp90 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 but not Hsp90 was associated with Bcl-2. Inhibition of Hsp90 suppressed the CpG-B ODN-induced association of Hsp90 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 but not Hsp90 in CpG-B ODN-mediated antiapoptotic response and that Hsp90 is distinct from Hsp90 in regulation of the cellular function of immune cells.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by grants from Academia Sinica (94F006) and the National Science Council (NSC93-2317-B-001-003) of Taiwan, Republic of China.

² Address correspondence and reprint requests to Dr. Shu-Mei Liang, Agricultural Biotechnology Research Center, Academia Sinica, 128 Academia Road, Section 2, Taipei, Taiwan; E-mail address: smyang{at}gate.sinica.edu.tw or Dr. Chi-Ming Liang, Institute of Biological Chemistry, Academia Sinica, 128 Academia Road, Section 2, Taipei, Taiwan; E-mail address: cmliang{at}gate.sinica.edu.tw

³ Abbreviations used in this paper: ODN, oligodeoxynucleotide; pDC, plasmacytoid dendritic cell; Hsp, heat shock protein; Apaf, apoptotic protease activation factor; siRNA, small interfering RNA; STS, staurosporine; DN, dominant negative; RNAi, RNA interference.