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Open AccessArticle

Anti-Inflammatory Effects of Spirulina platensis Extract via the Modulation of Histone Deacetylases

Department of Nutritional Sciences, University of Connecticut, Storrs, CT 06269, USA
Author to whom correspondence should be addressed.
Nutrients 2016, 8(6), 381;
Received: 11 April 2016 / Revised: 14 June 2016 / Accepted: 14 June 2016 / Published: 21 June 2016
We previously demonstrated that the organic extract of Spirulina platensis (SPE), an edible blue-green alga, possesses potent anti-inflammatory effects. In this study, we investigated if the regulation of histone deacetylases (HDACs) play a role in the anti-inflammatory effect of SPE in macrophages. Treatment of macrophages with SPE rapidly and dose-dependently reduced HDAC2, 3, and 4 proteins which preceded decreases in their mRNA levels. Degradation of HDAC4 protein was attenuated in the presence of inhibitors of calpain proteases, lysosomal acidification, and Ca2+/calmodulin-dependent protein kinase II, respectively, but not a proteasome inhibitor. Acetylated histone H3 was increased in SPE-treated macrophages to a similar level as macrophages treated with a pan-HDAC inhibitor, with concomitant inhibition of inflammatory gene expression upon LPS stimulation. Knockdown of HDAC3 increased basal and LPS-induced pro-inflammatory gene expression, while HDAC4 knockdown increased basal expression of interleukin-1β (IL-1β), but attenuated LPS-induced inflammatory gene expression. Chromatin immunoprecipitation showed that SPE decreased p65 binding and H3K9/K14 acetylation at the Il-1β and tumor necrosis factor α (Tnfα) promoters. Our results suggest that SPE increased global histone H3 acetylation by facilitating HDAC protein degradation, but decreases histone H3K9/K14 acetylation and p65 binding at the promoters of Il-1β and Tnfα to exert its anti-inflammatory effect. View Full-Text
Keywords: Spirulina platensis; histone deacetylases; anti-inflammatory; inflammation; epigenetics Spirulina platensis; histone deacetylases; anti-inflammatory; inflammation; epigenetics
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Pham, T.X.; Park, Y.-K.; Lee, J.-Y. Anti-Inflammatory Effects of Spirulina platensis Extract via the Modulation of Histone Deacetylases. Nutrients 2016, 8, 381.

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