CpG Protects Human Monocytic Cells against HIV-Vpr–Induced Apoptosis by Cellular Inhibitor of Apoptosis-2 through the Calcium-Activated JNK Pathway in a TLR9-Independent Manner

摘要: Monocytic cells survive HIV replication and consequent cytopathic effects because of their decreased sensitivity to HIV-induced apoptosis. However, the mechanism underlying this resistance apoptosis remains poorly understood. Lymphocytic are exposed microbial products translocation from gut in persons with chronic infections or following coinfections. We hypothesized that activation monocytic by such through interaction corresponding TLRs may confer antiapoptotic signals. Using HIV-viral protein R (Vpr)(52-96) peptide as a model apoptosis-inducing agent, we demonstrated unlike monocyte-derived macrophages, undifferentiated primary human monocytes promonocytic THP-1 highly susceptible Vpr(52-96)-induced Interestingly, stimulated TLR9 agonist CpG induced almost complete apoptosis, albeit TLR9-independent signaling pathway. Moreover, selectively cellular inhibitor (c-IAP)-2 inhibition c-IAP-2 gene either specific small interfering RNA synthetic second mitochondrial activator caspases mimetic reversed CpG-induced against Vpr(52-96)-mediated is regulated JNK calcium pathway, particular calmodulin-dependent kinase-II. Furthermore, including kinase-II pharmacological inhibitors RNAs protection also show phosphorylation Taken together, our results suggest be mediated calcium-activated pathway via what appeared pathways.