Anti-diabetic Drugs TZDs Inhibit NLRP3 Inflammasome Activation

The inflammasome is a cytosolic multimeric protein complex comprised of an intracellular sensor,the precursor pro-caspase-1 and adaptor ASC.Inflammasome complex is assembled in a pathogen-associated molecular pattern(PAMPs)or danger-associated molecular pattern(DAMPs)specific manner.It plays a key role in host defense against pathogen and inflammation.NLRP3,NLRC4,NLRP1,AIM2 are four types better studied inflammasomes in structures and components.Activation of the inflammasome triggers the caspase-1-dependent maturation and release of several pro-inflammatory cytokines,including interleukin-1?(IL-1?)and IL-18.Cytokine IL-1? is postulated to have an important role in the pathogensis of metabolic disorder.The metabolic syndrome is a cluster of conditions including central obesity,hyperglycemia,dyslipidemia and hypertension.Those factors may occur together,increasing the risk of metabolic disorders,including type 2 diabetes,atherosclerosis and gout.Low dose chronic inflammation is a key feature of metabolic disorders.Thiazolidinediones(TZDs),drugs widely used for the clinical to treatment for type 2 diabetes,enhance insulin sensitivity and lower blood glucose.Our results showed that the TZDs durgs including rosiglitazone and pioglitazone specifically inhibit NLRP3 inflammasome activation.Mechanismly,the rosiglitazone inhibited NLRP3 inflammasome activation via the disruption of the Asc oligomerization and ASC-Specks formation.