Many diseases accompanied by chronic inflammation are connected with dysregulated activation of macrophage subpopulations. Recently, we reported that nitro-fatty acids (NO2-FAs), products of metabolic and inflammatory reactions of nitric oxide and nitrite, modulate macrophage and other immune cell functions. Bone marrow cell suspensions were isolated from mice and supplemented with macrophage colony-stimulating factor (M-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF) in combination with NO2-OA for different times. RAW 264.7 macrophages were used for short-term (1-5min) experiments. We discovered that NO2-OA reduces cell numbers, cell colony formation, and proliferation of macrophages differentiated with colony-stimulating factors (CSFs), all in the absence of toxicity. In a case of GM-CSF-induced bone marrow-derived macrophages (BMMs), NO2-OA acts via downregulation of signal transducer and activator of transcription 5 and extracellular signal-regulated kinase (ERK) activation. In the case of M-CSF-induced BMMs, NO2-OA decreases activation of M-CSFR and activation of related PI3K and ERK. Additionally, NO2-OA also attenuates activation of BMMs. In aggregate, we demonstrate that NO2-OA regulates the process of macrophage differentiation and that NO2-FAs represent a promising therapeutic tool in the treatment of inflammatory pathologies linked with increased accumulation of macrophages in inflamed tissues.

Department of Pharmacology and Chemical Biology University of Pittsburgh Pittsburgh PA USA

Heart Centre University Hospital of Cologne Cologne Germany

Institute of Biophysics Academy of Sciences of the Czech Republic Brno Czechia

Institute of Biophysics Academy of Sciences of the Czech Republic Brno Czechia; International Clinical Research Center Center of Biomolecular and Cellular Engineering St Anne's University Hospital Brno Czechia

Institute of Biophysics Academy of Sciences of the Czech Republic Brno Czechia; International Clinical Research Center Center of Biomolecular and Cellular Engineering St Anne's University Hospital Brno Czechia; Department of Animal Physiology and Immunology Masaryk University Brno Czechia

International Clinical Research Center Center of Biomolecular and Cellular Engineering St Anne's University Hospital Brno Czechia; Heart Centre University Hospital of Cologne Cologne Germany

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