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Nutrients. 2016 Jun 21;8(6). pii: E381. doi: 10.3390/nu8060381.

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

Author information

1
Department of Nutritional Sciences, University of Connecticut, Storrs, CT 06269, USA. tho.pham@uconn.edu.
2
Department of Nutritional Sciences, University of Connecticut, Storrs, CT 06269, USA. young-ki.park@uconn.edu.
3
Department of Nutritional Sciences, University of Connecticut, Storrs, CT 06269, USA. ji-young.lee@uconn.edu.

Abstract

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 Ca(2+)/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.

KEYWORDS:

Spirulina platensis; anti-inflammatory; epigenetics; histone deacetylases; inflammation

PMID:
27338466
PMCID:
PMC4924221
DOI:
10.3390/nu8060381
[Indexed for MEDLINE]
Free PMC Article

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