CpG‐DNA Protects Against UV‐Induced Apoptosis Via Enhancement of AKT and mTORC1 in Keratinocytes And Dendritic Cells

Abstract

CpG‐DNA and its related synthetic CpG oligodeoxynucleotides (CpG‐ODNs) play an important role in immune cell survival and activation. Existing data have shown that AKT activation is involved in this process. However, the potential role of CpG‐ODN in protection against UV‐induced skin damage has thus far not been tested. In this study, we found that CpG‐ODN protects against UV‐induced cell death and apoptosis in both skin keratinocytes (HaCaT cells) and cultured dendritic cells (XS106, or DCs). In mechanism research, we found that CpG‐ODN pre‐treatment enhances UV induced activation of AKT (ser473, thr308 phosphorylation) as well as downstream signal TORC1 (S6K and 4E‐BP1 phosphorylation) in both HaCaT cells and DCs. AKT deficiency (by using AKT1/2 double knockout Mouse Embryonic Fibroblasts as well as LY 294002, a pharmacological inhibitors of AKT) or mTORC1 inhibition (by using rapamycin, a pharmacological inhibitor of mTORC1) largely neutralize the protective effects of CpG‐ODN, indicating that AKT and downstream signaling mTORC1 activation are necessary for CpG‐ODN induced protective effects against UV induced cell death. Our findings suggest that CpG‐ODN may be utilized to prevent from UV‐induced skin aging and provide a novel mechanism of protective effects against UV radiation.