Ethyl pyruvate (EP) is a redox-active compound that has been previously shown to be effective in restraining immune hyperactivity in animal models of various autoimmune and chronic inflammatory diseases. Importantly, EP has also been proven to have a potent tolerogenic effect on dendritic cells (DCs). Here, the influence of EP on the signaling pathways in DCs relevant for their tolerogenicity, including anti-inflammatory NRF2 and pro-inflammatory NF-κB, was explored.
View Article and Find Full Text PDFWe have recently characterized experimental autoimmune encephalomyelitis (EAE) induced in DA rats with spinal cord homogenate without complete Freund's adjuvant (CFA). The main advantage of this multiple sclerosis model is the lack of CFA-related confounding effects which represent the major obstacles in translating findings from EAE to multiple sclerosis. Here, antigen specificity of the cellular and humoral immune response directed against the central nervous system was explored.
View Article and Find Full Text PDFAcute respiratory distress syndrome (ARDS) became a focus of intensive research due to its death toll during the Covid-19 pandemic. An uncontrolled and excessive inflammatory response mediated by proinflammatory molecules such as high mobility group box protein 1 (HMGB1), IL-6, and TNF mounts as a response to infection. In this study, ethyl pyruvate (EP), a known inhibitor of HMGB1, was tested in the model of murine ARDS induced in C57BL/6 mice by intranasal administration of polyinosinic:polycytidylic acid (poly(I:C)).
View Article and Find Full Text PDFExperimental autoimmune encephalomyelitis (EAE) induced in inbred rodents, i.e., genetically identical animals kept under identical environmental conditions, shows variable clinical outcomes.
View Article and Find Full Text PDFInnate lymphoid cells type 3 (ILC3s) are the first line sentinels at the mucous tissues, where they contribute to the homeostatic immune response in a major way. Also, they have been increasingly appreciated as important modulators of chronic inflammatory and autoimmune responses, both locally and systemically. The proper identification of ILC3 is of utmost importance for meaningful studies on their role in immunity.
View Article and Find Full Text PDFRecent data indicate the link between the number and function of T regulatory cells (Treg) in the gut immune tissue and initiation and development of autoimmunity associated with type 1 diabetes (T1D). Since type 3 innate lymphoid cells (ILC3) in the small intestine are essential for maintaining FoxP3 Treg and there are no data about the possible role of ILC3 in T1D pathogenesis, the aim of this study was to explore ILC3-Treg link during the development of T1D. Mature diabetic NOD mice had lower frequencies of IL-2-producing ILC3 and Treg in small intestine lamina propria (SILP) compared to prediabetic NOD mice.
View Article and Find Full Text PDFGallic acid is a phenolic acid present in various plants, nuts, and fruits. It is well known for its anti-oxidative and anti-inflammatory properties. The phenethyl ester of gallic acid (PEGA) was synthesized with the aim of increasing the bioavailability of gallic acid, and thus its pharmacological potential.
View Article and Find Full Text PDFObjective: The study aimed to investigate acetylsalicylic acid (ASA) effects on osteo/odontogenic differentiation and proliferation of dental pulp stem cells (DPSCs) in vitro and the potential involvement of adenosine monophosphate-activated protein kinase (AMPK) pathway in these processes.
Design: DPSCs were isolated from third molars pulp tissues of five patients and grown in osteogenic medium alone or supplemented with ASA. Expression of DPSCs markers was tested by flow-cytometry.
Rosmarinic acid is a polyphenolic compound, abundantly present in herbs of the Lamiaceae family. The aim of the study was to evaluate the immunomodulatory properties of a recently developed phenethyl ester derivative of rosmarinic acid (PERA), with enhanced ability of diffusion through biological membranes, in an animal model of the central nervous system (CNS) autoimmunity. To this end, experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis was used.
View Article and Find Full Text PDFTwo Balkan Peninsula endemics, and subsp. , both characterized by specialized metabolite profiles predominated by iridoids and phenolics, are differentiated according to the stereochemistry of major iridoid aglycone nepetalactone (NL). For the first time, the present study provides a comparative analysis of antimicrobial and immunomodulating activities of the two species and their major iridoids isolated from natural sources--NL, -NL, and 1,5,9-epideoxyloganic acid (1,5,9-DLA), as well as of phenolic acid rosmarinic acid (RA).
View Article and Find Full Text PDFGut immune cells have been increasingly appreciated as important players in the central nervous system (CNS) autoimmunity in animal models of multiple sclerosis (MS). Among the gut immune cells, innate lymphoid cell type 3 (ILC3) is of special interest in MS research, as they represent the innate cell counterpart of the major pathogenic cell population in MS, T helper (Th)17 cells. Importantly, these cells have been shown to stimulate regulatory T cells (Treg) and to counteract pathogenic Th17 cells in animal models of autoimmune diseases.
View Article and Find Full Text PDFExperimental autoimmune encephalomyelitis (EAE) is classically induced with complete Freund's adjuvant (CFA). The immune response against CFA has a confounding influence on the translational capacity of EAE as a multiple sclerosis model. Here, we compare clinical, cellular and molecular properties between syngeneic spinal cord homogenate (SCH)- and SCH + CFA-immunized Dark Agouti rats.
View Article and Find Full Text PDFThe aim of this study was to examine the in vitro effects of the slow-releasing HS donor GYY4137 on the immune cells involved in the pathogenesis of the central nervous system (CNS) autoimmune disease, multiple sclerosis (MS). GYY4137 specifically potentiated TGF-β expression and production in dendritic cells and significantly reduced IFN-γ and IL-17 production in the lymph node and spinal cord T cells obtained from mice immunized with CNS antigens. Both the proportion of FoxP3 regulatory CD4 T cells in the lymph node cells, and the percentage of IL-17 CD4 T cells in the spinal cord cells were reduced upon culturing with GYY4137.
View Article and Find Full Text PDFAutoimmune diseases are progressively affecting westernized societies, as the proportion of individuals suffering from autoimmunity is steadily increasing over the past decades. Understanding the role of reactive oxygen species (ROS) in modulation of the immune response in the pathogenesis of autoimmune disorders is of utmost importance. The focus of this review is the regulation of ROS production within tolerogenic dendritic cells (tolDCs) and regulatory T (Treg) cells that have the essential role in the prevention of autoimmune diseases and significant potency in their therapy.
View Article and Find Full Text PDFDendritic cells (DC) are professional antigen presenting cells that have a key role in shaping the immune response. Tolerogenic DC (tolDC) have immuno-regulatory properties and they are a promising prospective therapy for multiple sclerosis and other autoimmune diseases. Ethyl pyruvate (EP) is a redox analog of dimethyl fumarate (Tecfidera), a drug for multiple sclerosis treatment.
View Article and Find Full Text PDFDendritic cells (DC) are responsible for the initiation and shaping of the adaptive immune response and are in the focus of autoimmunity research. We were interested in comparison of DC obtained from autoimmunity-prone Dark Agouti (DA) rats and autoimmunity-resistant Albino Oxford (AO) rats. DC were generated from bone marrow precursors and matured (mDC) by lipopolysaccharide.
View Article and Find Full Text PDFAlbino Oxford (AO) rats are extremely resistant to induction of experimental autoimmune encephalomyelitis (EAE). EAE is an animal model of multiple sclerosis, a chronic inflammatory disease of the central nervous system (CNS), with established autoimmune pathogenesis. The autoimmune response against the antigens of the CNS is initiated in the peripheral lymphoid tissues after immunization of AO rats with CNS antigens.
View Article and Find Full Text PDFEthyl pyruvate is a redox analogue of dimethyl fumarate (Tecfidera), a drug for multiple sclerosis treatment. We have recently shown that ethyl pyruvate ameliorates experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. It affects encephalitogenic T cells and macrophages in vitro, as well as in lymph nodes draining the site of encephalitogenic immunization and within the central nervous system (CNS).
View Article and Find Full Text PDFC57BL/6, BALB/c and NOD mice are among the most frequently used strains in autoimmunity research. NOD mice spontaneously develop type 1 diabetes (T1D) and they are prone to induction of experimental autoimmune encephalomyelitis (EAE). Both diseases can be routinely induced in C57BL/6 mice, but not in BALB/c mice.
View Article and Find Full Text PDFCucurbitacin E (CucE) is a highly oxidized steroid consisting of a tetracyclic triterpene. It is a member of a Cucurbitacin family of biomolecules that are predominantly found in Cucurbitaceae plants. CucE has already been identified as a potent anti-inflammatory compound.
View Article and Find Full Text PDFMicroRNAs (miR) are small non-coding RNAs involved in the immune response regulation. miR-155 has been attributed a major pro-inflammatory role in the pathogenesis of multiple sclerosis and its animal model experimental autoimmune encephalomyelitis (EAE). Here, a role of miR-155 in re-activation of encephalitogenic CD4(+) T cells was investigated.
View Article and Find Full Text PDFEthyl pyruvate (EP) has been increasingly appreciated as an anti-inflammatory and neuroprotective agent with potent pharmacological properties relevant for treatment of various CNS disorders. Microglial cells seem to be particularly sensitive to its effects. In this study, microglial cells were exposed to EP for relatively short periods (10-120min) and inflammatory properties of the cells were determined after 24h of cultivation.
View Article and Find Full Text PDFDimethyl fumarate (DMF), a new drug for multiple sclerosis (MS) treatment, acts against neuroinflammation via mechanisms that are triggered by adduct formation with thiol redox switches. Ethyl pyruvate (EP), an off-the-shelf agent, appears to be a redox analog of DMF, but its immunomodulatory properties have not been put into the context of MS therapy. In this article, we examined and compared the effects of EP and DMF on MS-relevant activity/functions of T cells, macrophages, microglia, and astrocytes.
View Article and Find Full Text PDFIt has been increasingly appreciated that tumor necrosis factor (TNF) performs various protective and anti-inflammatory functions in multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE). Recently, CXCL12 has been identified as a key inhibitor of leukocyte entry into the central nervous system (CNS) and as a regulator of inflammation resulting from the invasion. Here, a positive correlation between expression of TNF and CXCL12 in the CNS samples of EAE rats is presented.
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