Cobalt(II) Chloride Modifies the Phenotype of Macrophage Activation

• DOI: 10.1111/bcpt.12773
• Publication Date: 2017-02-28T06:32:41Z
• Authors: Mona Kumanto; Erja‐Leena Paukkeri; Riina Nieminen; Eeva Moilanen
• Keywords: Lipopolysaccharides; 0301 basic medicine; 0303 health sciences; Arginase; Interleukin-6; Gene Expression Profiling; Macrophages; Osmolar Concentration; Nitric Oxide Synthase Type II; Cobalt; Macrophage Activation; Hypoxia-Inducible Factor 1, alpha Subunit; Nitric Oxide; Cell Line; Trace Elements; Immunomodulation; Mice; 03 medical and health sciences; Gene Expression Regulation; NADPH Oxidase 2; Animals; Biomarkers

AbstractCobalt (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 CoCl2 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 (NOX2), interleukin‐6 (IL‐6), arginase‐1 and HIF‐1α. In the absence of exogenous cytokines, CoCl2 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, CoCl2 modified the M1‐type activation profile by increasing iNOS expression and nitric oxide production and decreasing NOX2 and IL‐6. Also, CoCl2 increased HIF‐1α levels in unstimulated and LPS‐stimulated cells as expected. In conclusion, we showed that CoCl2 enhanced alternative (M2) activation in resting macrophages. In addition, CoCl2 was found to remodel the classical M1 phenotype of macrophage activation by changing the balance of iNOS, NOX2 and IL‐6.