Monosodium urate crystals alter the circadian clock in macrophages leading to loss of NLRP3 inflammasome repression: Implications for timing of the gout flare

MSU crystal exposure resulted in altered expression of circadian clock components in THP-1 macrophages.

• BMAL1, CRY1, PER2, and REV-ERBα showed changes in expression with decreased protein levels of BMAL1 and REV-ERBα in macrophages after MSU crystal exposure.
• REV-ERBα activation or over-expression of BMAL1 led to reduced activity of the NLRP3 inflammasome, indicated by decreased caspase-1 activity.
• Knockdown of BMAL1 increased MSU crystal-induced caspase-1 activity, particularly during times of day when BMAL1 levels were naturally high.
• The greatest NLRP3 inflammasome activation in response to MSU crystals occurred at times of day when BMAL1 levels were naturally low.
• Alterations in circadian clock components in macrophages may contribute to the timing of gout flares and the associated inflammation.

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