ABSTRACT
The aim of this work was to study the effects of thymosin-1 alpha (Tα1) on the anti-inflammatory response of RAW 264.7 macrophages cultured in the presence of lipopolysaccharide (LPS) from the walls of gram-negative bacteria. As well, we evaluated production of pro-inflammatory cytokines and the activity of the NF-κB and SAPK/JNK signaling pathways. In addition, the level of expression of a number of genes that regulate cell apoptosis, as well as the activity of receptors involved in the pro-inflammatory response, was determined. First, the addition of Tα1 normalized the level of cytokine production to varying degrees, with a particularly noticeable effect on IL-1ß and IL-6. Second, the addition of Tα1 normalized the activity of the NF-κB and SAPK/JNK signaling cascades and the expression of the Tlr4 gene. Third, Tα1 significantly reduced p53 and the activity of the P53 gene, which is a marker of cell apoptosis. Fourth, it was shown that the increase in Ar-1 gene expression under the influence of LPS was significantly reduced using Tα1. Thus, it was found that the presence of Tα1 in the RAW 264.7 cell culture medium significantly reduced the level of the pro-inflammatory response of cells.
Subject(s)
NF-kappa B , Thymosin , Animals , Mice , NF-kappa B/genetics , NF-kappa B/metabolism , RAW 264.7 Cells , Endotoxins , Lipopolysaccharides/pharmacology , Thymosin/genetics , Thymosin/pharmacology , Cytokines/metabolismABSTRACT
This study aimed to assess the effects of the immunomodulator thymulin, a thymic peptide with anti-inflammatory effects, and peroxiredoxin 6 (Prdx6), an antioxidant enzyme with dual peroxidase and phospholipase A2 activities, on the bloodâbrain barrier (BBB) condition and general health status of animals with relapsing-remitting experimental autoimmune encephalomyelitis (EAE), which is a model of multiple sclerosis in humans. Both thymulin and Prdx6 significantly improved the condition of the BBB, which was impaired by EAE induction, as measured by Evans blue dye accumulation, tight-junction protein loss in brain tissue, and lymphocyte infiltration through the BBB. The effect was associated with significant amelioration of EAE symptoms. Thymulin treatment was accompanied by a decrease in immune cell activation as judged by interleukin-6, -17, and interferon-gamma cytokine levels in serum and NF-kappaB cascade activation in splenocytes of mice with EAE. Prdx6 did not induce significant immunomodulatory effects but abruptly decreased EAE-induced NOX1 and NOX4 gene expression in brain tissue, which may be one of the possible mechanisms of its beneficial effects on BBB conditions and health status. The simultaneous administration of thymulin and Prdx6 resulted in complete symptomatic restoration of mice with EAE. The results demonstrate prospective strategies for multiple sclerosis treatment.
Subject(s)
Encephalomyelitis, Autoimmune, Experimental , Multiple Sclerosis , Animals , Humans , Mice , Blood-Brain Barrier , Encephalomyelitis, Autoimmune, Experimental/drug therapy , Models, Theoretical , Multiple Sclerosis/drug therapy , Peroxiredoxin VI , Prospective Studies , Thymic Factor, Circulating/pharmacology , Thymic Factor, Circulating/therapeutic useABSTRACT
Antioxidant properties of recombinant peroxiredoxin-6 and chimeric protein PSH combining peroxidase and superoxide dismutase activities were studied on the model of retrograde perfusion of isolated rat heart under conditions of H2O2-induced oxidative stress. The exogenous antioxidant proteins exhibited cardioprotective properties manifested in heart rate normalization, maintenance of contractile activity of the myocardium, and prevention of H2O2-induced LPO in oxidative stress. Localization of peroxiredoxin-6 and PSH in the cardiac tissue was determined and myocardial structures most effectively protected by the antioxidant enzymes from ischemia/reperfusion-induced damages were identified. The results suggest that modified peroxiredoxins are promising components of perfusion media for preservation of isolated organs.
Subject(s)
Antioxidants/therapeutic use , Cardiotonic Agents/therapeutic use , Myocardial Reperfusion Injury/drug therapy , Myocardial Reperfusion Injury/prevention & control , Oxidative Stress/drug effects , Peroxiredoxins/therapeutic use , Animals , Heart/physiopathology , Heart Rate/drug effects , Hydrogen Peroxide/adverse effects , Male , Myocardial Contraction/drug effects , Perfusion , Peroxidase/metabolism , Rats , Rats, Wistar , Superoxide Dismutase/metabolismABSTRACT
The effect of negatively charged ions on respiratory organs and blood of rats has been studied. It was shown that the inhaling of negative air ions (NAI) for 60 min with a concentration of NAI at the place of location of animals 320-350 000 ions/cm2 activated the secretion of goblet cells without damaging the mucosa of the trachea and changed the spectrum of proteins of bronchopulmonary lavage. It was also found that the spontaneous production of reactive oxygen species (ROS) by cells of nonfractionated blood after the exposure to NAI increased in both males and females; the intensity of ROS generation induced by opsonized zymosan increased only in females. Different sensitivity of the antioxidant enzymes superoxide dismutase and glutathione reductase of blood to NAI in females and males was revealed. These results enable one to consider the effect of NAI as priming and a weak activation of the respiratory organs through the direct action on the mucosa of the primary target organs of the respiratory tract and then on the blood.
