69 research outputs found

    Outer membrane protein a of Salmonella enterica serovar Typhimurium activates dendritic cells and enhances Th1 polarization

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    <p>Abstract</p> <p>Background</p> <p>Typhoid, which is caused by <it>Salmonella enterica </it>serovar Typhimurium, remains a major health concern worldwide. Multidrug-resistant strains of <it>Salmonella </it>have emerged which exhibit increased survivability and virulence, thus leading to increased morbidity. However, little is known about the protective immune response against this microorganism. The outer membrane protein (Omp)A of bacteria plays an important role in pathogenesis.</p> <p>Results</p> <p>We purified OmpA from <it>S. enterica </it>serovar Typhimurium (OmpA-sal) and characterized the role of OmpA-sal in promoting adaptive and innate immune responses. OmpA-sal functionally activated bone marrow-derived dendritic cells by augmenting expression of CD80, CD86, and major histocompatibility complex classes I and II. Interestingly, OmpA-sal induced production of interferon-γ from T cells in mixed lymphocyte reactions, thus indicating Th1-polarizing capacity. The expression of surface markers and cytokine production in dendritic cells was mediated by the TLR4 signaling pathway in a TLR4 Knock-out system.</p> <p>Conclusions</p> <p>Our findings suggest that OmpA-sal modulates the adaptive immune responses to <it>S. enterica </it>serovar Typhimurium by activating dendritic cells and driving Th1 polarization, which are important properties to consider in the development of effective <it>S. enterica </it>serovar Typhimurium vaccines and immunotherapy adjuvant.</p

    Hepatoprotective and Antioxidative Activities of Cornus officinalis against Acetaminophen-Induced Hepatotoxicity in Mice

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    The fruit of Cornus officinalis Sieb. et Zucc. is commonly prescribed in Asian countries as a tonic formula. In this study, the hepatoprotective effect of ethanolic extracts of the fruit of C. officinalis (ECO) was investigated in a mouse model of acetaminophen- (APAP-) induced liver injury. Pretreatment of mice with ECO (100, 250, and 500 mg/kg for 7 days) significantly prevented the APAP (200 mg/kg) induced hepatic damage as indicated by the serum marker enzymes (AST, ALT, and LDH). Parallel to these changes, ECO treatment also prevented APAP-induced oxidative stress in the mice liver by inhibiting lipid peroxidation (MDA) and restoring the levels of antioxidant enzymes (SOD, CAT, and HO-1) and glutathione. Liver injury and collagen accumulation were assessed using histological studies by hematoxylin and eosin staining. Our results indicate that ECO can prevent hepatic injuries associated with APAP-induced hepatotoxicity by preventing or alleviating oxidative stress

    The Mycobacterium avium subsp. paratuberculosis fibronectin attachment protein, a toll-like receptor 4 agonist, enhances dendritic cell-based cancer vaccine potency

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    In this study, we showed the direct interaction between Mycobacterium avium subsp. paratuberculosis fibronectin attachment protein (FAP) and toll-like receptor4 (TLR4) via co-localization and binding by using confocal microscopy and co-immunoprecipitation assays. FAP triggered the expression of pro- and anti-inflammatory cytokines in a TLR4-dependent manner. In addition, FAP-induced cytokine expression in bone marrow-derived dendritic cells (BMDCs) was modulated in part by glycogen synthase kinase-3 (GSK-3). FAP-induced expression of CD80, CD86, major histocompatibility complex (MHC) class I, and MHC class II in TLR4+/+ BMDCs was not observed in TLR4-/- BMDCs. Furthermore, FAP induced DC-mediated CD8+ T cell proliferation and cytotoxic T lymphocyte (CTL) activity, and suppressed tumor growth with DC-based tumor vaccination in EG7 thymoma murine model. Taken together, these results indicate that the TLR4 agonist, FAP, a potential immunoadjuvant for DC-based cancer vaccination, improves the DC-based immune response via the TLR4 signaling pathway

    An Essential Regulatory Role of Downstream of Kinase-1 in the Ovalbumin-Induced Murine Model of Asthma

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    The downstream of kinase (DOK)-1 is involved in the protein tyrosine kinase (PTK) pathway in mast cells, but the role of DOK-1 in the pathogenesis of asthma has not been defined. In this study, we have demonstrated a novel regulatory role of DOK-1 in airway inflammation and physiologic responses in a murine model of asthma using lentiviral vector containing DOK-1 cDNA or DOK-1-specific ShRNA. The OVA-induced inflammatory cells, airway hyperresponsiveness, Th2 cytokine expression, and mucus response were significantly reduced in DOK-1 overexpressing mice compared to OVA-challenged control mice. The transgenic introduction of DOK-1 significantly stimulated the activation and expression of STAT-4 and T-bet, while impressively inhibiting the activation and expression of STAT-6 and GATA-3 in airway epithelial cells. On the other hand, DOK-1 knockdown mice enhanced STAT-6 expression and its nuclear translocation compared to OVA-challenged control mice. When viewed in combination, our studies demonstrate DOK-1 regulates allergen-induced Th2 immune responses by selective stimulation and inhibition of STAT-4 and STAT-6 signaling pathways, respectively. These studies provide a novel insight on the regulatory role of DOK-1 in allergen-induced Th2 inflammation and airway responses, which has therapeutic potential for asthma and other allergic diseases

    A Clinical Study on the Supracondylar Fractures of the Femur

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