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 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.


RESULTS
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.


CONCLUSIONS
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.


CONCLUSIONS
This study underscores natural products can exert anti-inflammatory effects by epigenetic modifications such as histone acetylation.
Department of Nutritional Sciences, University of Connecticut, Storrs, CT 06269, USA.
Chai Siah
CS
Ku
Tho X
TX
Pham
Youngki
Y
Park
Bohkyung
B
Kim
Min Sun
MS
Shin
Insoo
I
Kang
Jiyoung
J
Lee
D021581:Active Transport, Cell Nucleus; D000818:Animals; D002478:Cells, Cultured; D000458:Cyanobacteria / Q000502:physiology*; D016207:Cytokines / Q000096:biosynthesis*; D006655:Histone Deacetylases / Q000502:physiology; D006657:Histones / Q000378:metabolism; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D013154:Spleen / Q000166:cytology*
D016207:Cytokines; D006657:Histones; D016328:NF-kappa B; D006655:Histone Deacetylases