title: Anti-Inflammatory Effects of Spirulina platensis Extract via the Modulation of Histone Deacetylases.
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.
authors.affiliation: Department of Nutritional Sciences, University of Connecticut, Storrs, CT 06269, USA. tho.pham@uconn.edu.
authors.forename: Tho X
authors.initials: TX
authors.lastname: Pham
authors.affiliation: Department of Nutritional Sciences, University of Connecticut, Storrs, CT 06269, USA. young-ki.park@uconn.edu.
authors.forename: Young-Ki
authors.initials: YK
authors.lastname: Park
authors.affiliation: Department of Nutritional Sciences, University of Connecticut, Storrs, CT 06269, USA. ji-young.lee@uconn.edu.
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Lee
mesh_terms: D000107:Acetylation; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000032:analysis / Q000494:pharmacology*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000235:genetics / Q000378:metabolism; D047369:Chromatin Immunoprecipitation; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression; D056572:Histone Deacetylase Inhibitors / Q000032:analysis / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000378:metabolism*; D006657:Histones / Q000235:genetics / Q000378:metabolism; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D008247:Lysosomes / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D011401:Promoter Regions, Genetic; D000067996:RAW 264.7 Cells; D053545:Spirulina / Q000737:chemistry*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D006655:Histone Deacetylases
keywords: Spirulina platensis; anti-inflammatory; epigenetics; histone deacetylases; inflammation