Carbon monoxide regulates glycolysis-dependent NLRP3 inflammasome activation in macrophages
- Authors
- Lee, Do Won; Shin, Ha Young; Jeong, Ji Hun; Han, Jaeseok; Ryu, Seongho; Nakahira, Kiichi; Moon, Jong-Seok
- Issue Date
- 18-Nov-2017
- Publisher
- Academic Press
- Keywords
- CO; Glycolysis; NLRP3 inflammasome; Macrophages
- Citation
- Biochemical and Biophysical Research Communications, v.493, no.2, pp 957 - 963
- Pages
- 7
- Journal Title
- Biochemical and Biophysical Research Communications
- Volume
- 493
- Number
- 2
- Start Page
- 957
- End Page
- 963
- URI
- https://scholarworks.bwise.kr/sch/handle/2021.sw.sch/7042
- DOI
- 10.1016/j.bbrc.2017.09.111
- ISSN
- 0006-291X
1090-2104
- Abstract
- Low dose of carbon monoxide (CO) has anti-inflammatory role through various signaling pathways. Cellular metabolism has been implicated in the activation of inflammation in immune cells. However, the mechanisms by which CO-dependent metabolic regulation affect the immune response remain unclear. Here we show that CO-dependent metabolic pathway regulates the activation of the nucleotide-binding domain, leucine-rich-repeat-containing receptor (NLR), pyrin-domain-containing 3 (NLRP3) inflammasome. CO-releasing molecule-3 (CORM-3) resulted in reduced glycolysis-dependent NLRP3 inflammasome activation in macrophages. The reduced mTORC1 activation by CORM-3 resulted in less glycolysis during NLRP3 inflammasome activation. CORM-3 suppressed caspase-1 activation and the secretion of interleukin (IL)-1 beta and IL-18 in macrophages in response to lipopolysaccharide (LPS) and ATP. Moreover, CORM-3 inhibits the oligomerization of the adaptor protein apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), which is required for NLRP3-dependent caspase-1 activation. Furthermore, CORM-3-treated mice showed substantial reduction in IL-1 beta production by hyperglycemia in a mouse model of streptozotocin (STZ)-induced diabetes. Our results suggest that CO regulates glycolysis-dependent NLRP3 inflammasome activation and may provide a therapeutic approach for inflammation in metabolic diseases. (C) 2017 Elsevier Inc. All rights reserved.
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Collections - Graduate School > Department of Integrated Biomedical Science > 1. Journal Articles
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