Triglyceride induces DNA damage leading to monocyte death by activating caspase-2 and caspase-8

Abstract

Monocytes are peripheral leukocytes that function in innateimmunity. Excessive triglyceride (TG) accumulation causesmonocyte death and thus can compromise innate immunity. However, the mechanisms by which TG mediates monocytedeath remain unclear to date. Thus, this study aimed to elucidatethe mechanisms by which TG induces monocyte death. Results showed that TG induced monocyte death by activatingcaspase-3/7 and promoting poly (ADP-ribose) polymerase (PARP)cleavage. In addition, TG induced DNA damage and activatedthe ataxia telangiectasia mutated (ATM)/checkpoint kinase 2and ATM-and Rad3-related (ATR)/checkpoint kinase 1 pathways,leading to the cell death. Furthermore, TG-induced DNA damageand monocyte death were mediated by caspase-2 and -8,and caspase-8 acted as an upstream molecule of caspase-2. Taken together, these results suggest that TG-induced monocytedeath is mediated via the caspase-8/caspase-2/DNA damage/executioner caspase/PARP pathways.