Carbon monoxide regulates glycolysis-dependent NLRP3 inflammasome activation in macrophages
| Autor: | Ji Hun Jeong, Kiichi Nakahira, Ha young Shin, Seongho Ryu, Jong-Seok Moon, Do won Lee, Jaeseok Han |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male Inflammasomes Biophysics Inflammation mTORC1 Mechanistic Target of Rapamycin Complex 1 Biochemistry 03 medical and health sciences Mice NLR Family Pyrin Domain-Containing 3 Protein medicine Organometallic Compounds Animals Molecular Biology Caspase Carbon Monoxide biology Macrophages TOR Serine-Threonine Kinases Signal transducing adaptor protein Interleukin Inflammasome Cell Biology Cell biology Mice Inbred C57BL Metabolic pathway 030104 developmental biology Hyperglycemia Multiprotein Complexes biology.protein Signal transduction medicine.symptom Glycolysis medicine.drug |
| Zdroj: | Biochemical and biophysical research communications. 493(2) |
| ISSN: | 1090-2104 |
| Popis: | 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)-1β 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-1β 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. |
| Databáze: | OpenAIRE |
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