title: Triglyceride-induced macrophage cell death is triggered by caspase-1.
abstract: Triglyceride (TG) induces macrophage cell death which contributes to the development of atherosclerosis. We confirmed that exogenous TG accumulates in human THP-1 macrophages and causes cell death. TG treated THP-1 macrophages exhibited no change in tumor necrosis factor (TNF)-α, interleukin (IL)-18, macrophage inflammatory protein (MIP)-1α, and IL-1R1 receptor mRNA expression. However, there was a marked decrease in IL-1β mRNA expression but an increase in IL-1β protein secretion. Decreased expression of IL-1β mRNA and increased secretion of IL-1β protein was not the direct cause of cell death. Until now, TG was assumed to induce necrotic cell death in macrophages. Since caspase-1 is known to be involved in activation and secretion of IL-1β protein and pyroptotic cell death, next we determined whether caspase-1 is associated with TG-induced macrophage cell death. We found an increase in caspase-1 activity in TG-treated THP-1 macrophages and inhibition of caspase-1 activity using a specific inhibitor partially rescued cell death. These results suggest activation of the pyroptotic pathway by TG. This is the first report implicating the activation of caspase-1 and the triggering of the pyroptosis pathway in TG-induced macrophage cell death.
authors.affiliation: Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University, Wonju 220–710, Republic of Korea.
authors.forename: Sin Jee
authors.initials: SJ
authors.lastname: Son
authors.forename: Ki-Jong
authors.initials: KJ
authors.lastname: Rhee
authors.forename: Jaewon
authors.initials: J
authors.lastname: Lim
authors.forename: Tae Ue
authors.initials: TU
authors.lastname: Kim
authors.forename: Tack-Joong
authors.initials: TJ
authors.lastname: Kim
authors.forename: Yoon Suk
authors.initials: YS
authors.lastname: Kim
mesh_terms: D020170:Caspase 1 / Q000378:metabolism*; D016923:Cell Death / Q000502:physiology*; D002460:Cell Line; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D014280:Triglycerides / Q000494:pharmacology*
chemical_list: D053583:Interleukin-1beta; D012333:RNA, Messenger; D014280:Triglycerides; D020170:Caspase 1