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Interaction between NLRP3 Inflammasome and Sirt1/6 : Metabolomics Approach
Author(s) -
Lee Hee Jae,
Hong YoungShick,
Yang Soo Jin
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.913.12
Subject(s) - inflammasome , pyrin domain , sirtuin 1 , inflammation , chemistry , gene knockdown , sirtuin , receptor , nicotinamide , pharmacology , apoptosis , biochemistry , medicine , nad+ kinase , downregulation and upregulation , enzyme , gene
The aim of this study is to investigate the interaction between nucleotide binding and oligomerization domain‐like receptor family, pyrin domain containing 3 (NLRP3) inflammasome and sirtuin (Sirt) 1/6 and to evaluate the effects of nicotinamide riboside (NR) on NLRP3 inflammasome or Sirt 1/6. Recent studies have suggested that Sirt may have an anti‐inflammatory function. NLPR3 inflammasome amplifies pro‐inflammatory response and consists of NLRP3, apoptosis‐associated speck‐like protein containing a caspase activation recruitment domain (ASC), and caspase1. The interaction between NLPR3 inflammasome and Sirt1/6 relating to inflammation has remained unknown. NR, a new form of vitamin B3, presents in milk and beer. NR has been highlighted in advantageous effects on metabolic regulation. Knockdown (KD) technology for Sirt 1/6 and NLRP3 was applied, and then NR was administered. NLRP3 inflammasome complex (NLRP3, ASC, and caspase1), inflammatory markers, and Sirt pathway were analyzed. Serum metabolites of experimental mice were measured by 1 H NMR. KD of Sirt1 or 6 triggered hepatic metaflammation. Also, the levels of 3‐hydroxybutyrate and glutamate in serum were lower in Sirt1 KD group than control. Sirt1 KD activated NLRP3, ASC, and caspase1. However, NLRP3 KD did not alter the levels of Sirt and PGC1‐α. Administration of NR significantly improved pro‐inflammatory markers, including TNF‐α and IL‐6. These improvement was accompanied by significant shifts of NLRP3 inflammasome. NR intervention in NLRP3 KD mice ameliorated hepatic metaflammation. Serum metabolites were affected by NR treatment. Our results demonstrated that Sirt regulated NLRP3 inflammasome and NR affected NLRP3 inflammasome‐mediated hepatic metaflammation.