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Yang F.,CAS Institute of Zoology | Li Y.,CAS Institute of Zoology | Wu T.,CAS Institute of Zoology | Na N.,Sun Yat Sen University | And 5 more authors.
Journal of Molecular Medicine

Abstract: Efficient induction of functional competent myeloid-derived suppressor cells (MDSCs) will be critical for the clinical application of MDSCs to treat autoimmune diseases and to induce transplantation immune tolerance. In the present study, we tried to establish the MDSC induction system with M-CSF and tumor necrosis factor α (TNFα) and investigated the immunosuppressive function of M-CSF + TNFα-induced MDSCs in transplant mouse models. Monocytic MDSCs (M-MDSCs) were induced by culture of the non-adherent mouse bone marrow cells with M-CSF or M-CSF + TNFα, respectively, for 7 days. Phenotype analysis revealed that the majority of M-CSF- and M-CSF + TNFα-induced MDSCs express F4/80. The addition of TNFα in the induction period increased Gr-1, Ly6C, CD80, and CD274 expressions on these cells. M-CSF + TNFα-induced M-MDSCs showed poor TNFα, IL-12, and IL-6 expressions after lipopolysaccharide (LPS) stimulation and decreased arginase 1 (Arg-1) and Fizz expressions after IL-4 stimulation compared with M-CSF-induced M-MDSCs. M-CSF + TNFα-induced M-MDSCs showed enhanced ability to suppress T cell proliferation and cytokine production than M-CSF-induced M-MDSCs. M-CSF + TNFα-induced M-MDSCs express high levels of inducing nitric oxide synthase (iNOS) and blocking iNOS activity by a chemical inhibitor or gene deficiency significantly reversed the inhibitory effects of M-CSF + TNFα-induced M-MDSCs on T cells. Adoptive transfer of M-CSF + TNFα-induced M-MDSCs promoted immune tolerance in a male-to-female skin-grafted mice, but M-CSF + TNFα-induced iNOS-deficient M-MDSCs failed to do so. Thus, M-CSF + TNFα-induced M-MDSCs have powerful immunosuppressive activity, which is mediated by an iNOS-dependent pathway. M-CSF + TNFα-induced M-MDSCs can promote immune tolerance to donor antigens in a transplant mouse model. Key message: The combination of M-CSF and TNFα efficiently induces functional M-MDSCs in vitro.M-CSF + TNFα-induced M-MDSCs promote immune tolerance in a transplant mouse model.The immunosuppressive ability of M-CSF + TNFα-induced M-MDSCs is dependent on iNOS. © 2016 Springer-Verlag Berlin Heidelberg Source

Xiu J.-H.,Key Laboratory of Human Diseases Comparative Medicine | Zhu H.,Key Laboratory of Human Diseases Comparative Medicine | Xu Y.-F.,Institute of Laboratory Animal Science | Liu J.-N.,Key Laboratory of Human Diseases Comparative Medicine | And 2 more authors.
Virology Journal

Background: Enterovirus 71 (EV71) infections are associated with a high prevalence of hand, foot and mouth disease (HFMD) in children and occasionally cause lethal complications. Most infections are self-limiting. However, resulting complications, including aseptic meningitis, encephalitis, poliomyelitis-like acute flaccid paralysis, and neurological pulmonary edema or hemorrhage, are responsible for the lethal symptoms of EV71 infection, the pathogenesis of which remain to be clarified. Results: In the present study, 2-week-old Institute of Cancer Research (ICR) mice were infected with a mouse-adapted EV71 strain. These infected mice demonstrated progressive paralysis and died within 12 days post infection (d.p.i.). EV71, which mainly replicates in skeletal muscle tissues, caused severe necrotizing myositis. Lesions in the central nervous system (CNS) and other tissues were not observed. Conclusions: Necrotizing myositis of respiratory-related muscles caused severe restrictive hypoventilation and subsequent hypoxia, which could explain the fatality of EV71-infected mice. This finding suggests that, in addition to CNS injury, necrotic myositis may also be responsible for the paralysis and death observed in EV71-infected mice. © 2013 Xiu et al.; licensee BioMed Central Ltd. Source

Xiyang Y.-B.,Kunming Medical University | Ya-Zhao,Kunming Medical University | Lu B.-T.,Kunming Medical University | Ru J.,Kunming Medical University | And 5 more authors.
Biomedical Research (India)

As a growth regulator, PDGF-BB plays a crucial role in regulating neuronal survival and cell differentiation during embryonic development and in the adulthood. The multiple roles and mechanisms of PDGF-BB are still not known, especially involved in plasticity after spinal cord injury. However, before we can carry out further investigations a transgenic animal model with PDGF-BB down-regulation is needed. In the present study, expressional silencing PDGF-BB was achieved by select predesigning hairpins targeting mouse PDGF-BB genes. Six homozygous transgenic offspring were generated and the protein expressions of PDGF-BB were detected in multiple tissues of these mice. The down-regulated rates of PDGF-BB in different transgenic mice were also evaluated. Results showed that different PDGF-BB expressions were detected in multiple tissues and protein levels of PDGF-BB reduced at different rates by relative to that of wild type ones. The expressions of PDGF-BB proteins in transgenic mice decreased at most by 56%. The present study generated TG mice with PDGF-BB down-regulation and established mice model for systemic exploring the possible roles of PDGF-BB in vivo in different pathology conditions. Source

Wang W.,Peking Union Medical College | Wang W.,Chinese Academy of Sciences | Wang W.,Key Laboratory of Human Diseases Comparative Medicine | Wang W.,Key Laboratory of Human Diseases Animal Models | And 17 more authors.
AIDS Research and Therapy

Background: The precise efficacy of nucleoside analogue reverse-transcriptase inhibitors (NRTIs) in preventing and inhibiting virus replication remains unknown in RT-SHIV infected Chinese-origin rhesus macaques (Ch RM).Findings: Ch RM were inoculated intravenously with 200 TCID50 RT-SHIV and treated by gavage with NRTIs (20 mg AZT and 10 mg 3TC twice per day) for four consecutive weeks beginning at one hour, on day 217 or 297 post inoculation, respectively. Treatment with AZT/3TC inhibited transiently RT-SHIV replication during chronic infection, but did not significantly affect peripheral blood CD4+ T cells in macaques. Treatment with AZT/3TC at 1 hour post infection prevented RT-SHIV infection in two out of four animals during the 120-day observation period.Conclusions: Therefore, the Ch RM model with RT-SHIV infection can be used to evaluate the efficacy of new NRTIs. © 2014 Wang et al.; licensee BioMed Central Ltd. Source

Wang W.,Key Laboratory of Human Diseases Comparative Medicine | Wang W.,Key Laboratory of Human Diseases Animal Models | Wang W.,Chinese Academy of Sciences | Wang W.,Peking Union Medical College | And 22 more authors.
Journal of Medical Primatology

Background: Little is known about the comparative susceptibility and differential pathogenic characteristics of Chinese-origin rhesus macaques upon infection with the chimeric SHIVs most commonly applied in experimental research. Methods: In vivo infectivity, viral replication, and disease progression related to SHIV-1157ipd3N4, SHIV-162P3, and SHIV-KB9 infections were assessed after intravenous inoculation of Chinese-origin rhesus macaques (n = 10 each). Results: SHIV-KB9-infected monkeys had higher plasma viral loads than those infected with SHIV-1157ipd3N4 or SHIV-162P3 (P < 0.05). The SHIV-KB9 group had a member that progressed rapidly to simian acquired immunodeficiency syndrome and was moribund at 155 days post-inoculation. SHIV-KB9 and SHIV-162P3 showed reverse trends in the effects on levels of memory T-cell subpopulations. Conclusions: This study provides foundational data for future efficacy testing of candidate vaccine and antiviral therapy using a Chinese-origin rhesus macaque system. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. Source

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