beta-carotene and Gout

The NLRP3 inflammasome is closely linked to the pathophysiology of a wide range of inflammatory diseases. This study was undertaken to identify small molecules that directly bind to NLRP3 in order to develop pharmacologic interventions for NLRP3-related diseases.. A structure-based virtual screening analysis was performed with ~62,800 compounds to select efficient NLRP3 inhibitors. The production of caspase 1-p10 and interleukin-1β (IL-1β) was measured by immunoblotting and enzyme-linked immunosorbent assay to examine NLRP3 inflammasome activation. Two gouty arthritis models and an air pouch inflammation model induced by monosodium urate monohydrate (MSU) crystal injection were used for in vivo experiments. Primary synovial fluid cells from gout patients were used to determine the relevance of NLRP3 inflammasome inhibition in human gout.. Beta-carotene (provitamin A) suppressed the NLRP3 inflammasome activation induced by various activators, including MSU crystals, in mouse bone marrow-derived primary macrophages (P < 0.05). Surface plasmon resonance analysis demonstrated the direct binding of β-carotene to the pyrin domain (PYD) of NLRP3 (K. Our results present β-carotene as a selective and direct inhibitor of NLRP3, and the binding of β-carotene to NLRP3 PYD as a novel pharmacologic strategy to combat NLRP3 inflammasome-driven diseases, including gouty arthritis.

Topics: Animals; Arthritis, Gouty; beta Carotene; Caspase 1; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Gout; Humans; Inflammasomes; Inflammation; Interleukin-1beta; Macrophages; Mice; Molecular Docking Simulation; NLR Family, Pyrin Domain-Containing 3 Protein; Provitamins; Pyrin Domain; Surface Plasmon Resonance; Synovial Fluid