title: Cobalt(II) Chloride Modifies the Phenotype of Macrophage Activation.
abstract: Cobalt (Co) is vital for cells in trace amounts, but excessive exposure to Co is possible due to surgical devices such as artificial metal-on-metal joints. Cobalt(II) chloride (CoCl2) has also been shown to imitate hypoxic conditions in cells by stabilizing the transcription factor hypoxia-inducible factor-1α (HIF-1α). The purpose of this study was to investigate the possible immunomodulatory action of CoCl2by investigating its effects on the expression of inflammatory genes in macrophages. The following factors were assessed: inducible nitric oxidase synthase (iNOS), nicotinamide adenine dinucleotide phosphate-oxidase 2 (NOX2), interleukin-6 (IL-6), arginase-1 and HIF-1α. In the absence of exogenous cytokines, CoCl2enhanced alternative (M2) macrophage activation as demonstrated by increased arginase-1 expression, but had no direct effect on inflammatory factors associated with classical (M1) activation. Interestingly, in lipopolysaccharide (LPS)-stimulated macrophages, CoCl2modified the M1-type activation profile by increasing iNOS expression and nitric oxide production and decreasing NOX2 and IL-6. Also, CoCl2increased HIF-1α levels in unstimulated and LPS-stimulated cells as expected. In conclusion, we showed that CoCl2enhanced alternative (M2) activation in resting macrophages. In addition, CoCl2was found to remodel the classical M1 phenotype of macrophage activation by changing the balance of iNOS, NOX2 and IL-6.
authors.affiliation: The Immunopharmacology Research Group, Faculty of Medicine and Life Sciences, University of Tampere and Tampere University Hospital, Tampere, Finland.
authors.forename: Mona
authors.initials: M
authors.lastname: Kumanto
authors.affiliation: The Immunopharmacology Research Group, Faculty of Medicine and Life Sciences, University of Tampere and Tampere University Hospital, Tampere, Finland.
authors.forename: Erja-Leena
authors.initials: EL
authors.lastname: Paukkeri
authors.affiliation: The Immunopharmacology Research Group, Faculty of Medicine and Life Sciences, University of Tampere and Tampere University Hospital, Tampere, Finland.
authors.forename: Riina
authors.initials: R
authors.lastname: Nieminen
authors.affiliation: The Immunopharmacology Research Group, Faculty of Medicine and Life Sciences, University of Tampere and Tampere University Hospital, Tampere, Finland.
authors.forename: Eeva
authors.initials: E
authors.lastname: Moilanen
mesh_terms: D000818:Animals; D001119:Arginase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D002460:Cell Line; D003035:Cobalt / Q000494:pharmacology* / Q000506:poisoning; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D056747:Immunomodulation / Q000187:drug effects*; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity; D008262:Macrophage Activation / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D051379:Mice; D000074662:NADPH Oxidase 2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D009569:Nitric Oxide / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D009994:Osmolar Concentration; D014131:Trace Elements / Q000494:pharmacology* / Q000506:poisoning; D000093242:Interleukin-6 Inhibitors
chemical_list: D001119:Arginase; D015415:Biomarkers; D003035:Cobalt; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D015850:Interleukin-6; D008070:Lipopolysaccharides; D000074662:NADPH Oxidase 2; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D014131:Trace Elements; D000093242:Interleukin-6 Inhibitors; C497443:Hif1a protein, mouse; C577686:interleukin-6, mouse; C496317:Nos2 protein, mouse; C488842:Cybb protein, mouse; C544448:Arg1 protein, mouse; C018021:cobaltous chloride