Key Laboratory of Human Diseases Comparative Medicine

Key Laboratory of Human Diseases Comparative Medicine

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Wang P.,CAS Institute of Zoology | Wang P.,University of Chinese Academy of Sciences | Su H.,CAS Institute of Zoology | Su H.,University of Chinese Academy of Sciences | And 7 more authors.
Journal of Allergy and Clinical Immunology | Year: 2017

Background: Allergic asthma is one of the most common diseases worldwide, resulting in a burden of diseases. No available therapeutic regimens can cure asthma thus far. Objective: We sought to identify new molecular targets for TH9 cell-mediated allergic airway inflammation. Methods: Wild-type p53-induced phosphatase 1 (Wip1) gene knockout mice, Wip1 inhibitor-treated mice, and ovalbumin-induced allergic airway inflammation mouse models were used to characterize the roles of Wip1 in allergic airway inflammation. The induction of TH cell subsets in vitro, real-time PCR, immunoblots, luciferase assays, and chromatin immunoprecipitation assays were used to determine the regulatory pathways of Wip1 in TH9 differentiation. Results: Here we demonstrate that Wip1-deficient mice are less prone to allergic airway inflammation, as indicated by the decreased pathologic alterations in lungs. Short-term treatment with a Wip1-specific inhibitor significantly ameliorates allergic inflammation progression. Intriguingly, Wip1 selectively impaired TH9 but not TH1, TH2, and TH17 cell differentiation. Biochemical assays show that Wip1 deficiency increases c-Jun/c-Fos activity in a c-Jun N-terminal kinase-dependent manner and that c-Jun/c-Fos directly binds to Il9 promoter and inhibits Il9 transcription. Conclusion: Wip1 controls TH9 cell development through regulating c-Jun/c-Fos activity on the Il9 promoter and is important for the pathogenesis of allergic airway inflammation. These findings shed light on the previously unrecognized roles of Wip1 in TH9 cell differentiation. The inhibitory effects of a Wip1 inhibitor on the pathogenesis of allergic airway inflammation can have important implications for clinical application of Wip1 inhibitors in allergy therapies. © 2017.

Li Y.,Key Laboratory of Human Diseases Comparative Medicine | Li Y.,Chinese Academy of Sciences | Li Y.,Peking Union Medical College | Sui X.,Key Laboratory of Human Diseases Comparative Medicine | And 17 more authors.
Archives of Dermatological Research | Year: 2016

Henoch–Schönlein purpura (HSP) is a systemic vasculitis mediated by autologous immune complex. Animal models of HSP are scarce. Here, we describe the characteristics of HSP rabbit model in the acute and recovery phase. First, we constructed the HSP rabbit models, and then assessed immunologic indicators of models by enzyme-linked immunosorbent assay and immunoturbidimetry. Histomorphological characteristics were analyzed by haematoxylin–eosin, immunofluorescence and special staining. In the acute stage (24 h) after antigen challenge, the model group rabbits featured skin ecchymosis and abnormal laboratory examination results. Three weeks following the allergic reaction, purple spots improved markedly, and edema and blood seeping decreased, but obvious inflammation was present in the skin, kidneys, joints, gastrointestinal, lung and liver. Serological results of CD4, CD/CD8, IL-2, IL-4, and TNF-α, IgA, IgG, TropI, Alb and T were still abnormal. IgA and C3 expressed in skin and kidney and eosinophils expressed in skin and lungs were increased. The rabbit model can mimic human HSP lesions in symptoms, pathology, and immunology and may provide valuable insight into the pathogenesis of HSP and serve as a tool for future therapeutic development targeting HSP. © 2016 Springer-Verlag Berlin Heidelberg

Liu J.,Key Laboratory of Human Diseases Comparative Medicine | Dong W.,Key Laboratory of Human Diseases Comparative Medicine | Quan X.,Key Laboratory of Human Diseases Comparative Medicine | Ma C.,Institute of Laboratory Animal Science | And 4 more authors.
Archives of Virology | Year: 2012

Human PSGL-1 is a receptor for EV71 that facilitates EV71 entry and replication in mouse cells. We have evaluated the role of human PSGL-1 in EV71 infection in vivo using a transgenic mouse line. Expression of human PSGL-1 failed to enhance infectivity of clinical EV71 strains in mice; however, it promoted replication and symptom severity at an earlier stage in mice upon infection with a mouse-adapted EV71 strain. We therefore conclude that human PSGL-1 alone is not sufficient to modulate infection with the clinical EV71 strains of genotype C4 in mice. © 2011 Springer-Verlag.

Liu J.,Key Laboratory of Human Diseases Comparative Medicine | Li X.,Key Laboratory of Human Diseases Comparative Medicine | Fan X.,Key Laboratory of Human Diseases Comparative Medicine | Ma C.,Institute of Laboratory Animal Science | And 3 more authors.
Archives of Virology | Year: 2013

Human enterovirus 71 (EV71) causes hand, foot and mouth disease in children under 6 years of age, and the neurological complications of this virus can lead to death. Until now, no vaccines or drugs have been available for the clinical control of this epidemic. Macrophages can engulf pathogens and mediate a series of host immune responses that play a role in the defence against infectious diseases. Using immunohistochemistry, we observed the localizations of virus in muscle tissues of EV71-infected mice. The macrophages isolated from the adult mice could kill the virus gradually in vitro, as shown using quantitative real-time PCR (qRT-PCR) and virus titration. Co-localisation of lysosomes and virus within macrophages suggested that the lysosomes were possibly responsible for the phagocytosis of EV71. Activation of the macrophages in the peritoneal cavity of mice four days pre-infection reduced the mortality of mice upon lethal EV71 infection. The adoptive transfer of macrophages from adult mice inhibited virus replication in the muscle tissues of infected mice, and this was followed by a relief of symptoms and a significant reduction of mortality, which suggested that the adoptive transfer of macrophages from adult humans represents a potential strategy to treat EV71-infected patients. © 2012 Springer-Verlag Wien.

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 | Year: 2014

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.

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 | Year: 2016

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

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 | Year: 2013

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.

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) | Year: 2013

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.

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