Triglyceride-induced macrophage cell death is triggered by caspase-1

Sin Jee Son, Ki Jong Rhee, Jaewon Lim, Tae Ue Kim, Tack Joong Kim, Yoon Suk Kim

Research output: Contribution to journalArticle

6 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)108-113
Number of pages6
JournalBiological and Pharmaceutical Bulletin
Volume36
Issue number1
DOIs
Publication statusPublished - 2013 Jan 1

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All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmaceutical Science

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