| First Author | Lee DW | Year | 2017 |
| Journal | Biochem Biophys Res Commun | Volume | 493 |
| Issue | 2 | Pages | 957-963 |
| PubMed ID | 28942141 | Mgi Jnum | J:250870 |
| Mgi Id | MGI:6103472 | Doi | 10.1016/j.bbrc.2017.09.111 |
| Citation | Lee DW, et al. (2017) Carbon monoxide regulates glycolysis-dependent NLRP3 inflammasome activation in macrophages. Biochem Biophys Res Commun 493(2):957-963 |
| abstractText | 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)-1beta 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-1beta 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. |
