title: The immunomodulatory effects of barettin and involvement of the kinases CAMK1α and RIPK2.
abstract: BACKGROUND
  Barettin is a marine natural compound with reported anti-inflammatory and antioxidant properties. The combination of these effects led us to explore barettin further as an inhibitor of atherosclerosis development.
  
  
  METHODS
  The effect of barettin on MCP-1 and IL-10 secretion from activated immune cells was detected by ELISA. Determination of cell viability of oxidized low-density lipoprotein (oxLDL) and barettin exposed HUVEC cells were investigated by using CellTiter 96® AQ(ueous) One Solution. The kinase inhibition assays were performed using a radioactive ((33)P-ATP) filter binding assay at the University of Dundee, UK.
  
  
  RESULTS
  Barettin reduces the secretion of monocyte chemotactic protein-1 (MCP-1) from LPS-stimulated monocytes, but was not able to prevent oxLDL-induced cell death in HUVEC. Barettin has inhibitory activity against two protein kinases related to inflammation, namely the receptor-interacting serine/threonine kinase 2 (RIPK2) and calcium/calmodulin-dependent protein kinase 1α (CAMK1α). We also demonstrate that barettin reduce the production of the anti-inflammatory cytokine interleukin-10 (IL-10) in a dose and time-dependent manner, possibly by inhibiting CAMK1α.
  
  
  CONCLUSIONS
  The anti-inflammatory activity of barettin is exerted through the regulation of inflammatory mediators such as MCP-1 and IL-10, possibly via inhibition of kinases.
authors.affiliation: a Faculty of Biosciences , Fisheries and Economics, UiT The Arctic University of Norway , Tromsø , Norway .
authors.forename: Karianne Fredenfeldt
authors.initials: KF
authors.lastname: Lind
authors.affiliation: b Faculty of Health Sciences , UiT The Arctic University of Norway , Breivika , Tromsø , Norway , and.
authors.forename: Bjarne
authors.initials: B
authors.lastname: Østerud
authors.affiliation: c Marbio, UiT The Arctic University of Norway , Breivika , Tromsø , Norway.
authors.forename: Espen
authors.initials: E
authors.lastname: Hansen
authors.affiliation: a Faculty of Biosciences , Fisheries and Economics, UiT The Arctic University of Norway , Tromsø , Norway .
authors.forename: Trond Ø
authors.initials: TØ
authors.lastname: Jørgensen
authors.affiliation: c Marbio, UiT The Arctic University of Norway , Breivika , Tromsø , Norway.
authors.forename: Jeanette Hammer
authors.initials: JH
authors.lastname: Andersen
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D054729:Calcium-Calmodulin-Dependent Protein Kinase Type 1 / Q000037:antagonists & inhibitors / Q000276:immunology*; D045744:Cell Line, Tumor; D018932:Chemokine CCL2 / Q000276:immunology; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000276:immunology*; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology*; D016753:Interleukin-10 / Q000276:immunology; D010456:Peptides, Cyclic / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D053475:Receptor-Interacting Protein Serine-Threonine Kinase 2 / Q000037:antagonists & inhibitors / Q000276:immunology*
chemical_list: D000893:Anti-Inflammatory Agents; C111835:CCL2 protein, human; D018932:Chemokine CCL2; C508609:IL10 protein, human; D007155:Immunologic Factors; D010456:Peptides, Cyclic; D047428:Protein Kinase Inhibitors; C484472:barettin; D016753:Interleukin-10; C506253:RIPK2 protein, human; D053475:Receptor-Interacting Protein Serine-Threonine Kinase 2; C517596:CAMK1 protein, human; D054729:Calcium-Calmodulin-Dependent Protein Kinase Type 1
keywords: Antioxidant; IL-10; IL-1β; cytokines; marine natural compound