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The inhibition of class I histone deacetylases by butyrate can suppress acute gout arthritis

 

Acute gout arthritis is an inflammatory disease characterized by recurrent self-attacks on joint, caused by endogenously formed monosodium urate (MSU) crystals. MSU crystals are potent activators of the NLRP3 inflammasome, and together with long-chain free fatty acids (FFAs), they can mediate activation of cytokine interleukin (IL)-1β. On the other hand, Cleophas et al. found high concentration of short-chain fatty acid butyrate provides anti-inflammatory effect by inhibiting of histone deacetylases (HDACs) in acute gout arthritis. The article was published in Annals of the Rheumatic Diseases.

 

Researchers used peripheral blood mononuclear cells (PBMCs) freshly isolated from healthy donors, treated those cells with MSU crystals and palmitic acid in the presence or absence of short-chain fatty acid butyrate or HDAC inhibitor. They found butyrate has low cytokine inhibitory potency at mRNA level on class I HDACs, especially HDAC8. In contrast, several HDAC inhibitors showed potent effects of cytokine suppression at nanomolar concentrations, that could be effective in treatment of acute gout arthritis. 

 

Reference:
Ann Rheum Dis. 2015 Jan 14. pii: annrheumdis-2014-206258.

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