title: A heteroglycan from the cyanobacterium Nostoc commune modulates LPS-induced inflammatory cytokine secretion by THP-1 monocytes through phosphorylation of ERK1/2 and Akt.
abstract: Cyanobacteria (blue-green algae) have been consumed as food and used in folk medicine since ancient times to alleviate a variety of diseases. Cyanobacteria of the genus Nostoc have been shown to produce complex exopolysaccharides with antioxidant and antiviral activity. Furthermore, Nostoc sp. are common in cyanolichen symbiosis and lichen polysaccharides are known to have immunomodulating effects. Nc-5-s is a heteroglycan isolated from free-living colonies of Nostoc commune and its structure has been characterized in detail. The aim of this study was to determine the effects of Nc-5-s on the inflammatory response of lipopolysaccharide (LPS)-stimulated human THP-1 monocytes and how the effects are mediated. THP-1 monocytes primed with interferon-γ and stimulated with LPS in the presence of Nc-5-s secreted less of the pro-inflammatory cytokine interleukin (IL)-6 and more of the anti-inflammatory cytokine IL-10 than THP-1 monocytes stimulated without Nc-5-s. In contrast, Nc-5-s increased LPS-induced secretion of the pro-inflammatory cytokines tumor necrosis factor (TNF)-α and IL-8. Nc-5-s decreased LPS-induced phosphorylation of the extracellular regulated kinase (ERK)1/2 and Akt kinase, but did not affect phosphorylation of the p38 kinase, activation of the nuclear factor kappa B pathway, nor DNA binding of c-fos. These results show that Nc-5-s has anti-inflammatory effects on IL-6 and IL-10 secretion by THP-1 monocytes, but its effects are pro-inflammatory when it comes to TNF-α and IL-8. Furthermore, they show that the effects of Nc-5-s may be mediated through the ERK1/2 pathway and/or the Akt/phosphoinositide 3-kinase pathway and their downstream effectors. The ability of Nc-5-s to decrease IL-6 secretion, increase IL-10 secretion and moderate ERK1/2 activation indicates a potential for its development as an anti-inflammatory agent.
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Medicine, Biomedical Center, University of Iceland, Iceland; Department of Immunology, Faculty of Medicine, Biomedical Center, University of Iceland, Iceland; Center for Rheumatology Research, Landspitali - The National University Hospital of Iceland, Iceland; Department of Immunology, Landspitali - The National University Hospital of Iceland, Iceland.
authors.forename: Astridur
authors.initials: A
authors.lastname: Olafsdottir
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Medicine, Biomedical Center, University of Iceland, Iceland; Department of Immunology, Faculty of Medicine, Biomedical Center, University of Iceland, Iceland; Center for Rheumatology Research, Landspitali - The National University Hospital of Iceland, Iceland; Department of Immunology, Landspitali - The National University Hospital of Iceland, Iceland.
authors.forename: Gudny Ella
authors.initials: GE
authors.lastname: Thorlacius
authors.affiliation: Faculty of Pharmaceutical Sciences, University of Iceland, Iceland.
authors.forename: Sesselja
authors.initials: S
authors.lastname: Omarsdottir
authors.affiliation: Faculty of Pharmaceutical Sciences, University of Iceland, Iceland.
authors.forename: Elin Soffia
authors.initials: ES
authors.lastname: Olafsdottir
authors.affiliation: Center for Rheumatology Research, Landspitali - The National University Hospital of Iceland, Iceland.
authors.forename: Arnor
authors.initials: A
authors.lastname: Vikingsson
authors.affiliation: Department of Immunology, Faculty of Medicine, Biomedical Center, University of Iceland, Iceland; Center for Rheumatology Research, Landspitali - The National University Hospital of Iceland, Iceland; Department of Immunology, Landspitali - The National University Hospital of Iceland, Iceland.
authors.forename: Jona
authors.initials: J
authors.lastname: Freysdottir
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Medicine, Biomedical Center, University of Iceland, Iceland. Electronic address: ih@hi.is.
authors.forename: Ingibjorg
authors.initials: I
authors.lastname: Hardardottir
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002460:Cell Line; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008070:Lipopolysaccharides; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D009000:Monocytes / Q000187:drug effects*; D050501:Nostoc commune / Q000737:chemistry*; D010766:Phosphorylation; D011134:Polysaccharides / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; C508606:CXCL8 protein, human; C508609:IL10 protein, human; C508600:IL6 protein, human; D015850:Interleukin-6; D016209:Interleukin-8; D008070:Lipopolysaccharides; D011134:Polysaccharides; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D051057:Proto-Oncogene Proteins c-akt
keywords: IL-10 ERK1/2; IL-6; Nostoc commune; Polysaccharides; THP-1 cells