Edible blue-green algae reduce the production of pro-inflammatory cytokines by inhibiting NF-κB pathway in macrophages and splenocytes

• Published in: Biochimica et biophysica acta Vol. 1830; no. 4; pp. 2981 - 2988
• Main Authors: Ku, Chai Siah, Pham, Tho X., Park, Youngki, Kim, Bohkyung, Shin, Min Sun, Kang, Insoo, Lee, Jiyoung
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.04.2013
• Subjects: acetylation; Active Transport, Cell Nucleus; Animals; Anti-inflammation; anti-inflammatory activity; apolipoprotein E; Arthrospira platensis; atherosclerosis; Blue-green algae; Cells, Cultured; Cyanobacteria - physiology; Cytokine array; Cytokines - biosynthesis; diet; epigenetics; gene expression; gene expression regulation; histone deacetylase; Histone Deacetylases - physiology; Histone deacetylation; histones; Histones - metabolism; inflammation; insulin resistance; interleukin-1beta; interleukin-6; lipopolysaccharides; macrophages; Macrophages - immunology; messenger RNA; Mice; Mice, Inbred C57BL; NF-kappa B - antagonists & inhibitors; NF-κB; Nostoc commune; RAW 264.7 macrophage; secretion; Spirulina platensis; Spleen - cytology; splenocytes; transcription factor NF-kappa B; tumor necrosis factor-alpha; RAW 264.7 macrophage; NO; TNFα; Blue-green algae; apoE; SPE; LPS; Anti-inflammation; CBP; NF-κB; CREB; NLS; Histone deacetylation; BGA; SP; C-PC; BMM; IL; TSA; NOE; IκBα; CVD; HAT; Cytokine array; HDAC
• ISSN: 0304-4165; 0006-3002; 1872-8006
• DOI: 10.1016/j.bbagen.2013.01.018

Chronic inflammation contributes to the development of pathological disorders including insulin resistance and atherosclerosis. Identification of anti-inflammatory natural products can prevent the inflammatory diseases. Anti-inflammatory effects of blue-green algae (BGA), i.e., Nostoc commune var. sphaeroides Kützing (NO) and Spirulina platensis (SP), were compared in RAW 264.7 and mouse bone marrow-derived macrophages (BMM) as well as splenocytes from apolipoprotein E knockout (apoE−/−) mice fed BGA. When macrophages pretreated with 100μg/ml NO lipid extract (NOE) or SP lipid extract (SPE) were activated by lipopolysaccharide (LPS), expression and secretion of pro-inflammatory cytokines, such as tumor necrosis factor α (TNFα), interleukin 1β (IL-1β), and IL-6, were significantly repressed. NOE and SPE also significantly repressed the expression of TNFα and IL-1β in BMM. LPS-induced secretion of IL-6 was lower in splenocytes from apoE−/− fed an atherogenic diet containing 5% NO or SP for 12weeks. In RAW 264.7 macrophages, NOE and SPE markedly decreased nuclear translocation of NF-κB. The degree of repression of pro-inflammatory gene expression by algal extracts was much stronger than that of SN50, an inhibitor of NF-κB nuclear translocation. Trichostatin A, a pan histone deacetylase inhibitor, increased basal expression of IL-1β and attenuated the repression of the gene expression by SPE. SPE significantly down-regulated mRNA abundance of 11 HDAC isoforms, consequently increasing acetylated histone 3 levels. NOE and SPE repress pro-inflammatory cytokine expression and secretion in macrophages and splenocytes via inhibition of NF-κB pathway. Histone acetylation state is likely involved in the inhibition. This study underscores natural products can exert anti-inflammatory effects by epigenetic modifications such as histone acetylation. ► Anti-inflammatory effects of edible blue-green algae in macrophages ► Inhibition of NF-κB pathway for the anti-inflammatory effects in macrophages ► Repression of IL-6 secretion from splenocytes of mice fed blue-green algae ► Role of histone deacetylases in the anti-inflammatory role of blue-green algae