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Cobalt(II) Chloride Modifies the Phenotype of Macrophage Activation
Author(s) -
Kumanto Mona,
Paukkeri ErjaLeena,
Nieminen Riina,
Moilanen Eeva
Publication year - 2017
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/bcpt.12773
Subject(s) - arginase , nicotinamide adenine dinucleotide phosphate , lipopolysaccharide , chemistry , nitric oxide , macrophage , nitric oxide synthase , nadph oxidase , oxidase test , reactive oxygen species , polyamine oxidase , biochemistry , endocrinology , enzyme , biology , arginine , in vitro , organic chemistry , amino acid , spermine
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 (CoCl 2 ) 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 CoCl 2 by 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 ( NOX 2), interleukin‐6 ( IL ‐6), arginase‐1 and HIF ‐1α. In the absence of exogenous cytokines, CoCl 2 enhanced 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, CoCl 2 modified the M1‐type activation profile by increasing iNOS expression and nitric oxide production and decreasing NOX 2 and IL ‐6. Also, CoCl 2 increased HIF ‐1α levels in unstimulated and LPS ‐stimulated cells as expected. In conclusion, we showed that CoCl 2 enhanced alternative (M2) activation in resting macrophages. In addition, CoCl 2 was found to remodel the classical M1 phenotype of macrophage activation by changing the balance of iNOS , NOX 2 and IL ‐6.