Publications (12)41.22 Total impact
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Article: Hypothermia protects against oxygen-glucose deprivation-induced neuronal injury by down-regulating the reverse transport of glutamate by astrocytes as mediated by neurons.
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ABSTRACT: Glutamate is the major mediator of excitotoxic neuronal death following cerebral ischemia. Under severe ischemic conditions, glutamate transporters can functionally reverse to release glutamate, thereby inducing further neuronal injury. Hypothermia has been shown to protect neurons from brain ischemia. However, the mechanism(s) involved remain unclear. Therefore, the aim of this study was to investigate the mechanism(s) mediating glutamate release during brain ischemia-reperfusion injury under hypothermic conditions. Neuron/astrocyte co-cultures were exposed to oxygen-glucose deprivation (OGD) at various temperatures for 2 h, and cell viability was assayed 12 h after reoxygenation. PI and MAP-2 staining demonstrated that hypothermia significantly decreased neuronal injury. Furthermore, [(3)H]-glutamate uptake assays showed that hypothermia protected rat primary cortical cultures against OGD reoxygenation-induced injury. Protein levels of the astrocytic glutamate transporter, GLT-1, which is primarily responsible for the clearance of extracellular glutamate, were also found to be reduced in a temperature-dependent manner. In contrast, expression of GLT-1 in astrocyte-enriched cultures was found to significantly increase following the addition of neuron-conditioned medium maintained at 37 °C, and to a lesser extent with neuron-conditioned medium at 33 °C. In conclusion, the neuroprotective effects of hypothermia against brain ischemia-reperfusion injury involve down-regulation of astrocytic GLT-1, which mediates the reverse transport of glutamate. Moreover, this process may be regulated by molecules secreted by stressed neurons.Neuroscience 02/2013; · 3.38 Impact Factor -
Article: The mechanism of effective electroacupuncture on T cell response in rats with experimental autoimmune encephalomyelitis.
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ABSTRACT: Previously, we demonstrated that electroacupuncture (EA) decreased lymphocyte infiltration into the spinal cords of rats presenting with experimental autoimmune encephalomyelitis (EAE), a disease model used in the study of multiple sclerosis (MS). The aim of this study was to characterize the effects of EA on the EAE. Female Lewis rats were divided into either CFA, EAE, EA, or injection with naloxone after electroacupuncture (NAL) groups. Electroacupuncture was administered every day for 21 days. To evaluate proliferation and apoptosis, lymphocytes from rats presenting with EAE were collected and cultured with β-endorphin. Immunohistochemisty, flow cytometry and radio-immunity methods were applied to detect the expression of β-endorphin. Results presented in this report demonstrate that the beneficial anti-inflammatory effects of EA on EAE were related to β-endorphin production that balances the Thl/Th2 and Th17/Treg responses. These results suggest that β-endorphin could be an important component in the development of EA-based therapies used for the treatment of EAE.PLoS ONE 01/2013; 8(1):e51573. · 4.09 Impact Factor -
Article: Activation of the adenosine A2A receptor attenuates experimental autoimmune myasthenia gravis severity.
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ABSTRACT: The adenosine A2A receptor (A2AR) is the major cellular adenosine receptor commonly associated with immunosuppression. Here, we investigated whether A2AR activation holds the potential for impacting the severity of experimental autoimmune myasthenia gravis (EAMG) induced following immunization of Lewis rats with the acetylcholine receptor (AChR) R97-116 peptide. This report demonstrates reduced A2AR expression by both T cells and B cells residing in spleen and lymph nodes following EAMG induction. A2AR stimulation inhibited anti-AChR antibody production and proliferation of AChR-specific lymphocytes in vitro. Inhibition was blocked with the A2AR antagonists or protein kinase A inhibitor. We also determined that the development of EAMG was accompanied by a T-helper cell imbalance that could be restored following A2AR stimulation that resulted in increased Treg cell levels and a reduction in Th1-, Th2-, and Th17-cell subtypes. An EAMG-preventive treatment regimen was established that consisted of (2-(p-(2-carbonylethyl)phenylethylamino)-5-N-ethylcarboxamidoadenosine) (CGS21680; A2AR agonist) administration 1 day prior to EAMG induction. Administration of CGS21680 29 days post EAMG induction (therapeutic treatment) also ameliorated disease severity. We conclude that A2AR agonists may represent a new class of compounds that can be developed for use in the treatment of myasthenia gravis or other T-cell- and B-cell-mediated autoimmune diseases.European Journal of Immunology 05/2012; 42(5):1140-51. · 5.10 Impact Factor -
Article: Analysis of sirtuin 1 expression reveals a molecular explanation of IL-2-mediated reversal of T-cell tolerance.
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ABSTRACT: The type III histone deacetylase sirtuin 1 (Sirt1) is a suppressor of both innate and adoptive immune responses. We have recently found that Sirt1 expression is highly induced in anergic T cells. However, the transcriptional program to regulate Sirt1 expression in T cells remains uncharacterized. Here we report that the early responsive genes 2 and 3, which can be up-regulated by T-cell receptor-mediated activation of nuclear factor of activated T-cell transcription factors and are involved in peripheral T-cell tolerance, bind to the sirt1 promoter to transcript sirt1 mRNA. In addition, the forkhead transcription factor, FoxO3a, interacts with early responsive genes 2/3 on the sirt1 promoter to synergistically regulate Sirt1 expression. Interestingly, IL-2, a cytokine that can reverse T-cell anergy, suppresses sirt1 transcription by sequestering FoxO3a to the cytoplasm through activating the PI3K-AKT pathway. Expression of the constitutively active form of FoxO3a blocks IL-2-mediated reversal of T-cell tolerance by retaining sirt1 expression. Our findings here provide a molecular explanation of IL-2-mediated reversion of T-cell anergy.Proceedings of the National Academy of Sciences 01/2012; 109(3):899-904. · 9.68 Impact Factor -
Article: Activation of the receptor for advanced glycation end products (RAGE) exacerbates experimental autoimmune myasthenia gravis symptoms.
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ABSTRACT: RAGE belongs to immunoglobulin superfamily and serves as a ligand for various immunoregulatory molecules including S100B that has been demonstrated important to T cell mediated autoimmune diseases. In this context, we hypothesized that RAGE could also impact B cell mediated, T cell-dependent autoimmune diseases. This was tested using myasthenia gravis (MG) animal model, EAMG. We show that expression of both RAGE and S100B are increased during EAMG and the interaction between RAGE and S100B affected the Th1/Th2/Th17/Treg cell equilibrium, up-regulate AChR-specific T cell proliferation. Furthermore, addition of S100B in vitro stimulated splenocyte activity linked to COX-2 up-regulation. NS-398, a selective COX-2 inhibitor, effectively diminished S100B mediated activity of AChR-specific antibody secreting splenocytes. These findings suggested that a reciprocal relationship between RAGE and S100B promoted the development of EAMG, highlighting the importance of understanding the mechanisms of EAMG disease as a means of developing new therapies for the treatment of MG.Clinical Immunology 04/2011; 141(1):36-48. · 4.05 Impact Factor -
Article: Modeled microgravity suppressed expansion of the MBP-specific T lymphocytes of rats with experimental autoimmune encephalomyelitis.
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ABSTRACT: Experimental autoimmune encephalomyelitis (EAE) is characterized by uncontrolled proliferation of autoreactive T lymphocytes, with markedly increased secretion of pro-inflammatory cytokines. To further dissect the pathogenetic pathways of this disease, we exposed T lymphocytes from EAE rats, which were specific for myelin basic protein (MBP) to a modeled microgravity (MMG) environment, using a rotated cell culture system (RCCS) that was known to suppress proliferation of normal T cells. Following exposure to MMG, the proliferation of EAE lymphocytes decreased dramatically compared to those cultured in unit gravity (UG). At the beginning of MMG, a significant increase of apoptosis of MBP-specific T lymphocytes was observed, while at a later stage, the cytokine secretion profile of exposed MBP-specific T lymphocytes was altered, as was the differentiation of Th subsets. We concluded that the function of MBP-specific T lymphocytes was disordered after exposure to MMG.Immunological Investigations 01/2011; 40(5):535-51. · 1.47 Impact Factor -
Article: Malignant transformation of rat bone marrow-derived mesenchymal stem cells treated with 4-nitroquinoline 1-oxide.
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ABSTRACT: Recent studies indicated that extensive culture of bone marrow-derived mesenchymal stem cells (BMSCs) can lead to malignant transformation, supporting the concept that tumor may originate from adult stem cells. Also, neoplastic transformation of BMSCs induced by virus and ionizing radiation were verified. However, the capacity for BMSCs to become mutated by chemical carcinogens and become precursors of cancer is still poorly understood. In this study, BMSCs were used to test the hypothesis that tumorigenesis can originate from the mutation of stem cells induced by chemical carcinogen. BMSCs were intermittently treated with 10(-6)M 4-nitroquinoline 1-oxide (4-NQO) from population doublings level (PDL) 3 until senescence occurred. Proliferation data demonstrated that BMSCs treated with 4-NQO bypassed the senescence phase and exhibited unlimited proliferation and anchorage independence. These cells underwent a malignant transformation that resulted in tumor formation in 12/12 immunodeficient mice that received the cells by tail vein injection. In contrast, spontaneous transformation of BMSCs was observed in 6/12 immunodeficient mice injected with BMSCs that had been cultured over PDL 30 in vitro. For both BMSCs treated with 4-NQO, and BMSCs maintained in long-term culture, their transformation into neoplastic cells was found to involve chromosomal abnormalities, increased telomerase activity, and reduced, or absent, expression of p53. Our results also indicate that BMSCs are susceptible to carcinogen-induced malignant transformation rather than spontaneous transformation. Therefore, carcinogen-induced BMSCs transformation models may be ideal for studying mechanisms associated with the promotion of tumor formation by chemical carcinogens.Chemico-biological interactions 10/2010; 188(1):119-26. · 2.46 Impact Factor -
Article: Regulation of suppressing and activating effects of mesenchymal stem cells on the encephalitogenic potential of MBP68-86-specific lymphocytes.
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ABSTRACT: Mesenchymal stem cells (MSCs) possess immunosuppressive potential and are proposed as a tool for cell therapy, however under certain circumstance they could change to become immunostimulating. It is therefore of great importance to better understand the MSCs' immune plasticity. Here we used different doses of MSCs to co-culture with MBP(68-86)-specific T cells and found that MSCs exerted a suppressive effect on the encephalitogenic ability of MBP(68-86)-specific T cells at high MSC density (MSC/effector ratio ≥ 1:10). Whereas at lower MSC/effector ratios (≤ 1:50), MSCs shifted towards stimulatory activity. Thus the limited amounts of MSCs for application should be considered.Journal of neuroimmunology 09/2010; 226(1-2):116-25. · 2.84 Impact Factor -
Article: Disequilibrium of T helper type 1, 2 and 17 cells and regulatory T cells during the development of experimental autoimmune myasthenia gravis.
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ABSTRACT: Experimental autoimmune myasthenia gravis (EAMG), an animal model of myasthenia gravis (MG), is a rare organ-specific autoimmune disease targeting the autoantigen nicotinic acetylcholine receptor (AChR). We show here that the balance of T helper type 1 (Th1), Th2, Th17 and regulatory T (Treg) subsets of CD4(+) helper T cells were redistributed during the development of EAMG and that the interleukin-17 (IL-17) cytokine is involved in this disease. The ratio of Th17 cells changed most notably with disease progression accompanied by an up-regulated level of IL-17. Moreover, the proliferative ability of AChR peptide-specific T cells and the anti-AChR antibody-secreting cells increased when stimulated by IL-17 in vitro. These findings suggested that the disequilibrium of the CD4(+) helper T-cell subsets could promote the development of EAMG, and the pathogenic mechanism by which Th17 cells drives autoimmune responses by secreting cytokine IL-17 provides a new target for myasthenia gravis therapy.Immunology 09/2009; 128(1 Suppl):e826-36. · 3.32 Impact Factor -
Article: Simulated microgravity promotes cellular senescence via oxidant stress in rat PC12 cells.
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ABSTRACT: Microgravity has a unique effect on biological organisms. Organs exposed to microgravity display cellular senescence, a change that resembles the aging process. To directly investigate the influence of simulated microgravity on neuronal original rat PC12 cells, we used a rotary cell culture system that simulates the microgravity environment on the earth. We found that simulated microgravity induced partial G1 phase arrest, upregulated senescence-associated beta-galactosidase (SA-beta-gal) activity, and activated both p53 and p16 protein pathways linked to cell senescence. The amount of reactive oxygen species (ROS) was also increased. The activity of intracellular antioxidant enzymes, such as superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT), was all significantly increased at 12h after the microgravity onset, yet decreased at 96h. Furthermore, concomitant block of ROS by the antioxidant N-acetylcysteine significantly inhibited the microgravity-induced upregulation of SA-beta-gal activity. These results suggest that exposure to simulated microgravity induces cellular senescence in PC12 cells via an increased oxidant stress.Neurochemistry International 08/2009; 55(7):710-6. · 2.86 Impact Factor -
Article: TGF-beta expression by allogeneic bone marrow stromal cells ameliorates diabetes in NOD mice through modulating the distribution of CD4+ T cell subsets.
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ABSTRACT: BMSCs could promote the regeneration of islet beta-cell, but the status of BMSCs under diabetes is still unknown. Our study verified the effect of allogeneic BMSCs (ICR) transferred into NOD mice on blood glucose and CD4+ T cells subsets function. In vivo experiment, BMSCs could decrease blood glucose, weaken lymphocytes proliferation. In vitro experiment, the distribution of CD4+ T cell subsets was changed after co-culture with BMSCs, resulting in a greater frequency of Treg cells and reduced representation of Th17 cells. After TGF-beta blockade, CD4+ T cells differentiated along a route favoring development of Th17, but not Treg cells. Thus, NOD can be treated by BMSCs which changes the distribution of CD4+ T cells, increases the number of Treg cells, and inhibits the differentiation of Th17 cells. And the positive effects of allogeneic BMSCs in the treatment of NOD mice depend on the regulation of TGF-beta secreted by BMSCs.Cellular Immunology 08/2008; 253(1-2):23-30. · 1.97 Impact Factor -
Article: TGF-β expression by allogeneic bone marrow stromal cells ameliorates diabetes in NOD mice through modulating the distribution of CD4+ T cell subsets
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ABSTRACT: BMSCs could promote the regeneration of islet β-cell, but the status of BMSCs under diabetes is still unknown. Our study verified the effect of allogeneic BMSCs (ICR) transferred into NOD mice on blood glucose and CD4+ T cells subsets function. In vivo experiment, BMSCs could decrease blood glucose, weaken lymphocytes proliferation. In vitro experiment, the distribution of CD4+ T cell subsets was changed after co-culture with BMSCs, resulting in a greater frequency of Treg cells and reduced representation of Th17 cells. After TGF-β blockade, CD4+ T cells differentiated along a route favoring development of Th17, but not Treg cells. Thus, NOD can be treated by BMSCs which changes the distribution of CD4+ T cells, increases the number of Treg cells, and inhibits the differentiation of Th17 cells. And the positive effects of allogeneic BMSCs in the treatment of NOD mice depend on the regulation of TGF-β secreted by BMSCs.Cellular Immunology.
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Institutions
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2009–2013
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Harbin Medical University
Harbin, Heilongjiang Sheng, China
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