Can uric acid (Uric) kidney stones activate the NLRP3 (Nucleotide-binding domain, leucine-rich repeat-containing family, pyrin domain-containing 3) inflammasome?

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From the Research

Uric Acid and NLRP3 Inflammasome Activation

• Uric acid is a damage-associated molecular pattern (DAMP) that can activate the NLRP3 inflammasome, leading to the production of IL-1β and other pro-inflammatory molecules 1.
• Soluble uric acid (sUA) can also activate the NLRP3 inflammasome, even before the formation of crystals, and induce the production of IL-1β and caspase-1 activation 1, 2.
• The activation of the NLRP3 inflammasome by uric acid is associated with various diseases, including gout, metabolic syndrome, and kidney injuries 3.

Mechanisms of Uric Acid-Induced NLRP3 Inflammasome Activation

• Uric acid can induce the production of mitochondrial ROS, which contributes to the activation of the NLRP3 inflammasome 1, 2.
• The activation of the NLRP3 inflammasome by uric acid is also associated with the elevation of TLR6 levels and the activation of the NF-κB/p65 signal pathway 2.
• The interaction between uric acid and the NLRP3 inflammasome can lead to the activation of caspase-1 and the production of mature IL-1β, which can cause cell damage and death 4.

Uric Acid and Kidney Disease

• Hyperuricemia is an independent risk factor for the progression of chronic kidney disease, and uric acid can activate the NLRP3 inflammasome in the kidney, leading to inflammation and fibrosis 3, 4, 5.
• The activation of the NLRP3 inflammasome by uric acid in the kidney is associated with the epithelial-mesenchymal transition (EMT) and the production of pro-inflammatory molecules 5.