ABSTRACT
Differences in peritoneal macrophage polarization in mice of opposite lines CBA and C57Bl/6 and the effects of 60 kDa oxidized dextran were studied. Macrophages of C57Bl/6 mice demonstrated a phenotype close to M1, with increasing expression of CD86 costimulatory molecule and unchanged CD206 expression in response to activation. Macrophages of CBA mice demonstrated higher plasticity in response to activating agents; expression of the markers increased irrespectively on stimulated receptor (TLR-4 or mannose receptor) and both CD86 (classical activation) and CD206 (alternative activation) increased. Macrophage response to addition of oxidized dextran (60 kDa) to the culture medium could be characterized as potentiation of their alternative activation: expression of CD86 in CBA mice in response to LPS and LPS+IL-4 and in C57Bl/6 mice in response to IFN-γ and LPS+IFN-γ decreased, while expression of CD206 by intact macrophages of CBA mice and by macrophages stimulated by IFN-γ and IL-4 increased under the effect of 60 kDa oxidized dextran.
Subject(s)
Adjuvants, Immunologic/pharmacology , Dextrans/pharmacology , Macrophages, Peritoneal/drug effects , Animals , Cell Polarity , Drug Evaluation, Preclinical , Lectins, C-Type/metabolism , Lipopolysaccharides/pharmacology , Macrophage Activation/drug effects , Macrophages, Peritoneal/immunology , Macrophages, Peritoneal/metabolism , Male , Mannose Receptor , Mannose-Binding Lectins/metabolism , Mice, Inbred C57BL , Mice, Inbred CBA , Receptors, Cell Surface/metabolismABSTRACT
We studied the effects of liposomal pharmaceutical compositions with oxidized dextrans on functional activity of U937 monocyte/macrophage-like cells. Liposomes in the emulsion contained oxidized dextran with a molecular weights of 40 kDa or 70 kDa or isonicotinic acid hydrazide (INAH) conjugated with oxidized dextran (40 kDa). Cell viability was evaluated by MTT test; mitochondrial transmembrane potential and production of superoxide anion and H2O2 were studied by fluorescent methods. The studied compositions exhibited no cytotoxic effect and even improved cell viability and mitochondrial respiration. Liposomes with oxidized 40 kDa dextran, including those with INAH-conjugated dextran, inhibited production of superoxide anion, but increased H2O2 generation.
Subject(s)
Antitubercular Agents/pharmacology , Dextrans/pharmacology , Isoniazid/pharmacology , Macrophages/drug effects , Cell Survival , Dextrans/administration & dosage , Dextrans/chemistry , Dose-Response Relationship, Drug , Emulsions , Humans , Hydrogen Peroxide/metabolism , Liposomes , Membrane Potential, Mitochondrial/drug effects , Mitochondria/drug effects , Molecular Weight , Oxidation-Reduction , Oxidative Stress/drug effects , Phosphatidylcholines , Superoxides/metabolism , U937 CellsABSTRACT
We studied ROS production by HaCaT keratinocytes, the state of transmembrane mitochondrial potential, and activation of transcription factor Nrf2 in response to brine exposure. It was demonstrated that this exposure induces rapid but moderate decrease in mitochondrial potential, stimulates ROS production, and leads to activation of transcription factor Nrf2.
Subject(s)
Keratinocytes/metabolism , Keratinocytes/physiology , Membrane Potential, Mitochondrial/physiology , NF-E2-Related Factor 2/metabolism , Reactive Oxygen Species/metabolism , Salts/pharmacology , Cell Differentiation/drug effects , Cell Line , Flow Cytometry , Fluorescent Antibody Technique , Humans , Keratinocytes/drug effects , Membrane Potential, Mitochondrial/drug effects , Oxidation-ReductionABSTRACT
The protective effect of partially substituted monophenol TS-13 inducing the Nrf2/Keap1/ARE signaling system was studied on the model of chronic inflammation in vivo. It was found that during simulation of inflammation in an air pouch lined with synovial-like membrane, TS-13 did not affect the exudate volume, protein content, and cell count, but significantly reduced the intensity of oxidative metabolism in leukocytes of the exudate. In rheumatoid polyarthritis induced by heterologous collagen, TS-13 reduced the severity of clinical signs of inflammation only at the early stages, but inhibited H2O2 generation by monocytes and, partially, by blood neutrophils. These results suggest that the phlogolytic effect of the redox sensitive Nrf2/Keap1/ARE signaling system is less pronounced in chronic immune-mediated inflammatory processes than in acute inflammation.
Subject(s)
Antioxidant Response Elements/physiology , Arthritis, Rheumatoid/drug therapy , Inflammation/prevention & control , Signal Transduction/physiology , Thiosulfonic Acids/pharmacology , Animals , Antioxidant Response Elements/drug effects , Arthritis, Rheumatoid/chemically induced , Collagen/adverse effects , Flow Cytometry , Hydrogen Peroxide/metabolism , Leukocytes/drug effects , Male , Oxidation-Reduction , Rats , Rats, Wistar , Signal Transduction/drug effects , Statistics, NonparametricABSTRACT
The protective effect of water-soluble TS-13 monophenol inducing the antioxidant-responsive element (ARE) system was studied on the models of acute inflammation. Intragastric administration of TS-13 to rats significantly reduced the severity of acute aseptic inflammation induced by intravenous injection of zymosan particles: granulocyte blood count and volume density of infiltrates in the liver decreased on day 3, spontaneous production of activated oxygen metabolites and respiratory burst in blood granulocytes decreased on days 2 and 3. A single dose of TS-13 improved survival of mice with endotoxin shock induced by intraperitoneal injection of E. coli LPS. These results confirmed high anti-inflammatory activity of TS-13.
