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Colchicine-related effects on gene and protein expression in gout
Will T Mitchell1, Austin M Wheeler1,2
1University of Nebraska Medical Center.
Purpose Of Review:
Gout is an inflammatory arthritis mediated by monosodium urate deposition in synovial tissue. Colchicine is a common treatment for acute gout flares and prophylaxis, with well established efficacy but an incompletely understood mechanism. Investigating colchicine's impact at a proteomic and transcriptomic level may highlight these mechanisms. Interest in colchicine's effect on atherosclerotic cardiovascular disease (ASCVD) has stimulated additional research in this area.
Recent Findings:
Proteomic studies have helped identify gout's inflammatory signature, supporting prior evidence of nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasome activation and involvement of inflammatory signaling pathways. Comparing recent 'omics studies between gout and colchicine use in ASCVD models reveals an overlap in inflammatory pathways. Colchicine reduced innate immune system activation in four separate ASCVD models, with notable overlap in mediators of the NLRP3 inflammasome [interleukin (IL)-1β, IL-6, IL-18, and monocyte chemotactic protein-1] and others.
Summary:
Building on recent studies of colchicine's effect in ASCVD and the overlap seen with pathways implicated in gout, proteomic and transcriptomic studies in gout could further our understanding of the mechanisms driving colchicine's effectiveness. A more complete understanding of colchicine's mechanisms of action in gout may help guide future efforts at development of more targeted approaches to gout treatment.
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