Edible blue-green algae reduce the production of pro-inflammatory cytokines by inhibiting NF-κB pathway in macrophages and splenocytes
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. s...
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| Published in | Biochimica et biophysica acta Vol. 1830; no. 4; pp. 2981 - 2988 |
|---|---|
| Main Authors | , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Netherlands
Elsevier B.V
01.04.2013
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| Abstract | 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 |
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| AbstractList | 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. CONCLUSION: 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. GENERAL SIGNIFICANCE: This study underscores natural products can exert anti-inflammatory effects by epigenetic modifications such as histone acetylation. 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 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.BACKGROUNDChronic 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.METHODSAnti-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.RESULTSWhen 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.CONCLUSIONNOE 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.GENERAL SIGNIFICANCEThis study underscores natural products can exert anti-inflammatory effects by epigenetic modifications such as histone acetylation. 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. 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. |
| Author | Pham, Tho X. Kang, Insoo Ku, Chai Siah Park, Youngki Shin, Min Sun Lee, Jiyoung Kim, Bohkyung |
| AuthorAffiliation | 1 Department of Nutritional Sciences, University of Connecticut, Storrs, CT 06269 2 Department of Internal Medicine, Yale University School of Medicine, New haven, CT 06520 |
| AuthorAffiliation_xml | – name: 1 Department of Nutritional Sciences, University of Connecticut, Storrs, CT 06269 – name: 2 Department of Internal Medicine, Yale University School of Medicine, New haven, CT 06520 |
| Author_xml | – sequence: 1 givenname: Chai Siah surname: Ku fullname: Ku, Chai Siah organization: Department of Nutritional Sciences, University of Connecticut, Storrs, CT 06269, USA – sequence: 2 givenname: Tho X. surname: Pham fullname: Pham, Tho X. organization: Department of Nutritional Sciences, University of Connecticut, Storrs, CT 06269, USA – sequence: 3 givenname: Youngki surname: Park fullname: Park, Youngki organization: Department of Nutritional Sciences, University of Connecticut, Storrs, CT 06269, USA – sequence: 4 givenname: Bohkyung surname: Kim fullname: Kim, Bohkyung organization: Department of Nutritional Sciences, University of Connecticut, Storrs, CT 06269, USA – sequence: 5 givenname: Min Sun surname: Shin fullname: Shin, Min Sun organization: Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA – sequence: 6 givenname: Insoo surname: Kang fullname: Kang, Insoo organization: Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA – sequence: 7 givenname: Jiyoung surname: Lee fullname: Lee, Jiyoung email: Ji-young.lee@uconn.edu organization: Department of Nutritional Sciences, University of Connecticut, Storrs, CT 06269, USA |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/23357040$$D View this record in MEDLINE/PubMed |
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| PublicationDecade | 2010 |
| PublicationPlace | Netherlands |
| PublicationPlace_xml | – name: Netherlands |
| PublicationTitle | Biochimica et biophysica acta |
| PublicationTitleAlternate | Biochim Biophys Acta |
| PublicationYear | 2013 |
| Publisher | Elsevier B.V |
| Publisher_xml | – name: Elsevier B.V |
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| SubjectTerms | 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 |
| Title | Edible blue-green algae reduce the production of pro-inflammatory cytokines by inhibiting NF-κB pathway in macrophages and splenocytes |
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