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Free Radic Biol Med. 2017 Mar;104:10-19. doi: 10.1016/j.freeradbiomed.2017.01.003. Epub 2017 Jan 4.

Nitro-oleic acid regulates growth factor-induced differentiation of bone marrow-derived macrophages.

Author information

1
Institute of Biophysics, Academy of Sciences of the Czech Republic, Brno, Czechia.
2
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.
3
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.
4
Heart Centre, University Hospital of Cologne, Cologne, Germany.
5
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.
6
Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA, USA.
7
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. Electronic address: pekarovam@ibp.cz.

Abstract

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.

KEYWORDS:

Differentiation; Growth factors; Inflammation; Macrophages; Nitro-fatty acids; Nitro-oleic acid; Signaling pathways

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