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

Background: 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. Methods: Anti-inflammatory effects of blue-green algae (BGA), i.e., Nostoc commune var. sphaeroides Kutzing (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. Results: When macrophages pretreated with 100 mu g/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 alpha (TNF alpha), interleukin 1 beta (IL-1 beta), and IL-6, were significantly repressed. NOE and SPE also significantly repressed the expression of TNF alpha and IL-1 beta in BMM. LPS-induced secretion of IL-6 was lower in splenocytes from apoE(-/-) fed an atherogenic diet containing 5% NO or SP for 12 weeks. In RAW 264.7 macrophages, NOE and SPE markedly decreased nuclear translocation of NF-kappa B. The degree of repression of pro-inflammatory gene expression by algal extracts was much stronger than that of SN50, an inhibitor of NF-kappa B nuclear translocation. Trichostatin A, a pan histone deacetylase inhibitor, increased basal expression of IL-1 beta 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. Conclusion: NOE and SPE repress pro-inflammatory cytokine expression and secretion in macrophages and splenocytes via inhibition of NF-kappa B pathway. Histone acetylation state is likely involved in the inhibition. General significance: This study underscores natural products can exert anti-inflammatory effects by epigenetic modifications such as histone acetylation. (C) 2013 Elsevier B.V. All rights reserved.