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중성지방에 의한 대식세포 사멸 과정에서 Cathepsin B의 영향

Cathepsin B Is Implicated in Triglyceride (TG)-Induced Cell Death of Macrophage

대한임상검사과학회지 2020년 52권 3호 p.245 ~ 252
Jung Byung-Chul, 임재원, 김성훈, 김윤숙,
소속 상세정보
 ( Jung Byung-Chul ) - University of California Department of Nutritional Sciences and Toxicology
임재원 ( Lim Jae-Won ) - Yonsei University College of Health Science Department of Biomedical Laboratory Science
김성훈 ( Kim Sung-Hoon ) - Yonsei University College of Health Science Department of Biomedical Laboratory Science
김윤숙 ( Kim Yoon-Suk ) - Yonsei University College of Health Science Department of Biomedical Laboratory Science

Abstract


Macrophage cell death contributes to the formation of plaque, leading to the development of atherosclerosis. The accumulation of triglyceride (TG) is also associated with the pathogenesis of atherosclerosis. A previous study reported that TG induces the cell death of macrophages. This study examined whether the cytoplasmic release of cathepsin B from lysosome is associated with the TG-induced cell death of macrophage. The release of cathepsin B was increased in the TG-treated THP-1 macrophages, but the TG treatment did not affect cathepsin B expression. Furthermore, the inhibition of cathepsin B by its inhibitor, CA-074 Me, partially inhibited the TG-induced cell death of macrophage. TG-triggered macrophage cell death is mediated by the activation of caspase-1, -2, and apoptotic caspases. Therefore, this study investigated whether cathepsin B is implicated in the activation of these caspases. The inhibition of cathepsin B blocked the activation of caspase-7, -8, and -1 but did not affect the activity of caspase-3, -9, and -2. Overall, these results suggest that TG-induced cytoplasmic cathepsin B causes THP-1 macrophage cell death by activating caspase-1, leading to subsequent activation of the extrinsic apoptotic pathway.

키워드

Caspase-1; Cathepsin B; Cell death; THP-1 macrophage; Triglyceride

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