title: Nitro-oleic acid regulates growth factor-induced differentiation of bone marrow-derived macrophages.
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.
authors.affiliation: Institute of Biophysics, Academy of Sciences of the Czech Republic, Brno, Czechia.
authors.forename: Hana
authors.initials: H
authors.lastname: Verescakova
authors.affiliation: 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.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Ambrozova
authors.affiliation: 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.
authors.forename: Lukas
authors.initials: L
authors.lastname: Kubala
authors.affiliation: 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.
authors.forename: Tomas
authors.initials: T
authors.lastname: Perecko
authors.affiliation: 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.
authors.forename: Adolf
authors.initials: A
authors.lastname: Koudelka
authors.affiliation: 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.
authors.forename: Ondrej
authors.initials: O
authors.lastname: Vasicek
authors.affiliation: Heart Centre, University Hospital of Cologne, Cologne, Germany.
authors.forename: Tanja K
authors.initials: TK
authors.lastname: Rudolph
authors.affiliation: 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.
authors.forename: Anna
authors.initials: A
authors.lastname: Klinke
authors.affiliation: Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Steven R
authors.initials: SR
authors.lastname: Woodcock
authors.affiliation: Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Freeman
authors.affiliation: 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.
authors.forename: Michaela
authors.initials: M
authors.lastname: Pekarova
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D003115:Colony-Stimulating Factors / Q000235:genetics*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D007249:Inflammation / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D009569:Nitric Oxide / Q000008:administration & dosage* / Q000737:chemistry; D019301:Oleic Acid / Q000008:administration & dosage* / Q000737:chemistry; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D000067996:RAW 264.7 Cells; D050799:STAT5 Transcription Factor / Q000235:genetics
chemical_list: D003115:Colony-Stimulating Factors; D050799:STAT5 Transcription Factor; D019301:Oleic Acid; D009569:Nitric Oxide; D019869:Phosphatidylinositol 3-Kinases; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Differentiation; Growth factors; Inflammation; Macrophages; Nitro-fatty acids; Nitro-oleic acid; Signaling pathways