Return to study ST002378 main page
MB Sample ID: SA237400
| Local Sample ID: | GSDMD-LPS-2 |
| Subject ID: | SU002467 |
| Subject Type: | Cultured cells |
| Subject Species: | Mus musculus |
| Taxonomy ID: | 10090 |
| Gender: | Male and female |
Select appropriate tab below to view additional metadata details:
Treatment:
| Treatment ID: | TR002479 |
| Treatment Summary: | WT and GSDMD KO bone marrow derived macrophages were first primed with 300 ng/ml LPS (E. coli 0111; B4, Sigma-Aldrich) before stimulated with or without 5 mM ATP (Sigma-Aldrich) for 30 min in the presence or absence of 10 uM JX06. Here, we show that pharmacological or genetic inhibition of pyruvate dehydrogenase kinase (PDHK) significantly attenuates NLRP3 inflammasome activation in murine and human macrophages and septic mice by lowering caspase-1 cleavage and IL-1beta secretion. Inhibiting PDHK reverses NLRP3 inflammasome-induced metabolic reprogramming, enhances autophagy, promotes mitochondrial fusion over fission, preserves cristae ultrastructure, and attenuates mitochondrial ROS production. The suppressive effect of PDHK inhibition on the NLRP3 inflammasome is independent of its canonical role as a pyruvate dehydrogenase regulator. We suggest that PDHK inhibition improves mitochondrial fitness by reversing NLRP3 inflammasome activation in acutely inflamed macrophages. |
| Treatment: | In vitro culture |
| Treatment Compound: | LPS, ATP, JX06 |
