PI3K/AKT Mediated p53 Down-Regulation Participates in CpG DNA Inhibition of Spontaneous B Cell Apoptosis

• Published in: Cellular & molecular immunology Vol. 6; no. 3; pp. 175 - 180
• Main Authors: Zhou, Yongxin, Zhen, Huiling, Mei, Yunqing, Wang, Yongwu, Feng, Jing, Xu, Shuchang, Fu, Xiaoying
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.06.2009; Nature Publishing Group; Department of Thoracic-Cardiovascular Surgury,Tongji Hospital,Tongji University,Shanghai 200065,China%Department of Gastroenterology, Tongii Hospital Tongji University,Shanghai 200065,China
• Subjects: 1-Phosphatidylinositol 3-kinase; AKT protein; Androstadienes - pharmacology; Animals; Antibodies; Apoptosis; B-Lymphocytes - cytology; B-Lymphocytes - drug effects; B-Lymphocytes - metabolism; Bcl-x protein; bcl-X Protein - metabolism; Biomedical and Life Sciences; Biomedicine; Blotting, Western; Bone Marrow Cells - cytology; Bone Marrow Cells - drug effects; Bone Marrow Cells - metabolism; caspase; Caspase 3 - metabolism; Caspase-3; Cells, Cultured; Chromones - pharmacology; CpG islands; CpG基序; Deoxyribonucleic acid; DNA; DNA序列; Dose-Response Relationship, Drug; Down-Regulation - drug effects; Enzyme Inhibitors - pharmacology; Flow Cytometry; Immunology; Inhibitor of Apoptosis Proteins - metabolism; Kinases; Lymphocytes B; Macrophages - cytology; Macrophages - drug effects; Macrophages - metabolism; Medical Microbiology; Mice; Mice, Inbred C57BL; Microbiology; Morpholines - pharmacology; p53 Protein; p53基因; Phosphatidylinositol 3-Kinases - antagonists & inhibitors; Phosphatidylinositol 3-Kinases - metabolism; Phosphorothioate Oligonucleotides - pharmacology; Proto-Oncogene Proteins c-akt - metabolism; Signal Transduction - drug effects; Tumor Suppressor Protein p53 - metabolism; Up-Regulation - drug effects; Vaccine; Wortmannin; 激酶活性; 细胞凋亡; CpG DNA; apoptosis; AKT; PI3K; p53; Key Words: CpG DNA
• ISSN: 1672-7681; 2042-0226
• DOI: 10.1038/cmi.2009.24

The unmethylated CpG DNA can prevent spontaneous apoptosis of B cells. However, the precise mechanisms by which CpG DNA blocks apoptosis remain unclear. In this study, we showed B cell apoptosis was significantly inhibited by addition of CpG DNA. Treatment of CpG DNA could reduce the expression of caspase 3, increase IAP and Bcl-xL expressions, and inhibit p53 protein expression which level was increased in B cell spontaneous apoptosis at 24 h. AKT kinase activity was increased with the incubation of CpG DNA. The wortmannin and Ly294002 could abrogate the protection of B cell from apoptosis by CpG DNA. The up-regulations of Bcl-xL and IAP by CpG DNA were not inhibited when blocking PI3K by specific inhibitor Ly294002, while the inhibition of p53 by CpG DNA could be blocked by Ly294002. These results demonstrated that the inhibition of spontaneous B cell apoptosis by CpG DNA was correlated to up-regulation of Bcl-xL, IAP and down-regulation of p53 and caspase 3. CpG DNA inhibition of p53 is mediated through PI3K/AKT signaling.