Browsing by Subject "Mouse model"
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- PublicationEmbargoArtemisia pollen is the main vector for airborne endotoxin(Elsevier, 2018-08-09) Oteros, José; Bartusel, Elke; Alessandrini, Francesca; Núñez, Andrés; Moreno, Diego A.; Behrendt, Heidrun; Schmidt-Weber, Carsten; Traidl-Hoffmann, Claudia; Buters, Jeroen; Genética y MicrobiologíaBackground: Endotoxin (LPS) released from gram-negative bacteria causes strong immunologic and inflammatory effects and, when airborne, can contribute to respiratory conditions, such as allergic asthma. Objectives: We sought to identify the source of airborne endotoxin and the effect of this endotoxin on allergic sensitization. Methods: We determined LPS levels in outdoor air on a daily basis for 4 consecutive years in Munich (Germany) and Davos (Switzerland). Air was sampled as particulate matter (PM) greater than 10 μm (PM > 10) and PM between 2.5 and 10 μm. LPS levels were determined by using the recombinant Factor C assay. Results: More than 60% of the annual endotoxin exposure was detected in the PM > 10 fraction, showing that bacteria do not aerosolize as independent units or aggregates but adhered to large particles. In Munich 70% of annual exposure was detected between June 12th and August 28th. Multivariate modeling showed that endotoxin levels could be explained by phenological parameters (ie, plant growth). Indeed, days with high airborne endotoxin levels correlated well with the amount of Artemisia pollen in the air. Pollen collected from plants across Europe (100 locations) showed that the highest levels of endotoxin were detected on Artemisia vulgaris (mugwort) pollen, with little on other pollen. Microbiome analysis showed that LPS concentrations on mugwort pollen were related to the presence of Pseudomonas species and Pantoea species communities. In a mouse model of allergic disease, the presence of LPS on mugwort pollen was needed for allergic sensitization. Conclusions: The majority of airborne endotoxin stems from bacteria dispersed with pollen of only one plant: mugwort. This LPS was essential for inducing inflammation of the lung and allergic sensitization.
- PublicationEmbargoCharacterization of a murine model of intranasal infection suitable for testing vaccines against C. abortus(Elsevier, 2007-01-15) Buendía, A. J.; Nicolás, L.; Ortega, N.; Gallego, M. C.; Martínez Cáceres, Carlos Manuel; Sánchez, J.; Caro, M. R.; Navarro, J. A.; Salinas, J.; Anatomía y Anatomía Patológica ComparadaMouse models have been widely used to test candidate vaccines against Chlamydophila abortus infection in mice. Although the induction of a systemic infection by endogenous or intraperitoneal inoculation is a useful tool for understanding the immune mechanism involved in the protection conferred by the vaccination, a different approach is necessary to understand other factors of the infection, such as mucosal immunity or the colonization of target organs. To test whether C. abortus intranasal model of infection in mice is a useful tool for testing vaccines in a first group of experiments mice, were infected intranasally with C. abortus to characterize the model of infection. When this model was used to test vaccines, two inactivated experimental vaccines, one of them adjuvated with QS-21 and another with aluminium hydroxide, and a live attenuated vaccine (strain 1B) were used. Non-vaccinated control mice died within the first 8 days, after displaying substantial loss of weight. Histologically, the mice showed lobar fibrinopurulent bronchointerstitial pneumonia. Prior immunization with QS-21 adjuvated vaccine or 1B vaccine presented mortality and the recipients showed a greater number of T cells in the lesions, especially CD8+ T cells, than the control mice and mice immunized with vaccine adjuvated with aluminium hydroxide. The results confirm that the C. abortus intranasal model of infection in mice is a useful tool for testing vaccines
- PublicationOpen AccessCharacterization of the early pathology of cochlear stereocilia in four inbred mouse strains with progressive hearing loss(Universidad de Murcia. Departamento de Biología Celular e Histología, 2019) Liu, Xiang; Xie, Yi; Huang, Shanshan; Xu, Ang; Zhao, Mengmeng; Kang, Xiaoxia; Yan, Aiwei; Li, Ping; Jin, Changzhu; Han, FengchanObjective. Inbred strains of mice offer promising models for understanding the genetic basis of age-related hearing loss (AHL). NOD/LtJ, A/J, DBA/2J and C57BL/6J mice are classical models of age-related hearing loss and exhibit early onset of pathology of AHL. This study was carried out to characterize the early pathology of cochlear stereocilia in the four mouse strains with age-related hearing loss. Methods. The structural features of stereocilia in NOD/LtJ, A/J, DBA/2J and C57BL/6J mice were observed by scanning electron microscopy (SEM) at age of 2, 4, 6 or 8, and 10 or 12 weeks. Meanwhile, auditoryevoked brainstem response (ABR) and distortion product otoacoustic emission (DPOAE) amplitudes of the mice were measured at various intervals (3, 4, 6, 8, 10 and 12 weeks of age). Results. The ABR thresholds in NOD/LtJ, A/J and DBA/2J mice increased with age from 3 to 12 weeks. DPOAE amplitudes in NOD/LtJ, A/J, DBA/2J mice were very low at 4 weeks and became negative at 8 weeks at f2 frequency of 17 672 Hz. In addition to the progressive hearing loss, the four mouse strains displayed early onset (at 2 weeks of age) and progressive degeneration of stereocilia in hair cells. Conclusion. Early degeneration of stereocilia contributes to the functional impairment of hair cells and hearing loss in NOD/LtJ, A/J, DBA/2J and C57BL/6J mice.
- PublicationOpen AccessIL-10 Overexpression Reduces the Protective Response of an Experimental Chlamydia abortus Vaccine in a Murine Model(MDPI, 2024-08-12) Del Río, Laura; Salinas, Jesús; Ortega, Nieves; Buendía, Antonio J.; Navarro, José A.; Caro, María Rosa; Sanidad Animal; Anatomía y Anatomía Patológica ComparadaIn ovine populations, the enzootic nature of Chlamydia abortus (C. abortus) is attributed to its capacity to establish persistent intracellular infections, which necessitate a cellular immune response mediated by interferon-gamma (IFN-γ) for effective resolution. In both natural hosts and murine models, interleukin-10 (IL-10) has been demonstrated to modulate the cellular immune response crucial for the eradication of C. abortus. During gestation, it has also been shown to play a role in preventing inflammatory damage to gestational tissues and foetal loss through the downregulation of pro-inflammatory cytokines. This paradigm can be key for events leading to a protective response towards an infectious abortion. Previous research successfully established a mouse model of chronic C. abortus infection using transgenic mice overexpressing IL-10 (IL-10tg), simulating the dynamics of chronic infection observed in non-pregnant natural host. This study aims to evaluate the efficacy of an experimental inactivated vaccine against C. abortus and to elucidate the immune mechanisms involved in protection during chronic infection using this model. Transgenic and wild-type (WT) control mice were immunized and subsequently challenged with C. abortus. Vaccine effectiveness and immune response were assessed via immunohistochemistry and cytokine serum levels over a 28-day period. Morbidity, measured by daily weight loss, was more pronounced in non-vaccinated transgenic IL-10 mice, though no mortality was observed in any group. Vaccinated control mice eliminated the bacterial infection by day 9 post-infection (p.i.), whereas presence of bacteria was noted in vaccinated transgenic IL-10 mice until day 28 p.i. Vaccination induced an early post-infection increase in IFN-γ production, but did not alter IL-10 production in transgenic mice. Histological analysis indicated suboptimal recruitment of inflammatory cells in vaccinated transgenic IL-10 mice compared to WT controls. In summary, the findings suggest that IL-10 overexpression in transgenic mice diminishes the protective efficacy of vaccination, confirming that this model can be useful for validating the efficacy of vaccines against intracellular pathogens such as C. abortus that require robust cell-mediated immunity.
- PublicationOpen AccessInbred wild type mouse strains have distinct spontaneous morphological phenotypes(F. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología, 2013) Serpi, Raisa; Klein-Rodewald, Tanja; Calzada-Wack, Julia; Neff, Frauke; Schuster, Tibor; Gailus-Durner, Valérie; Fuchs, Helmut; Poutanen, Matti; Hrabé de Angelis, Martin; Esposito, IreneThe mouse is the most commonly used animal for modelling human disease. New approaches for generating genetically manipulated mouse models to represent human disease, as well as target the function of specific genes, has increased the importance of mice in biomedical science. For the correct interpretation of alterations in mouse phenotype the basic morphology of background mouse strains must be known. Despite ongoing efforts to create publicly available baseline phenotypic data, the information concerning spontaneous lesions in wild-type mice is incomplete and scattered so far, and further studies are needed. We addressed this problem by screening haematoxylin-eosin stained sections of brain, reproductive organs, urinary bladder, kidney, thyroid, parathyroid, heart, lung, spleen, thymus, lymph nodes, adrenal glands, stomach, intestine, liver, skin and pancreas of six commonly used inbred mouse strains (C57BL6/J, C57BL6/NTac, C3HeB/FeJ, BALB/cByJ, 129P2/OlaHsd and FVB/N) for inherent spontaneous morphological lesions. Interesting spontaneous phenotypes were seen in morphology of the liver, pancreas, adrenal glands, lungs, intestines and heart. In conclusion, care should be taken when choosing the background mouse strain for genetic manipulations, since different mouse strains harbour different inherent lesions that can affect the function of targeted genes, interpretation of results and translation of results to model human disease.
- PublicationEmbargoProtective role of antithrombin in mouse models of liver injury(Elsevier, 2012) Guerrero, José A; Teruel, Raul; Martínez, Constantino; Arcas, Isabel; Martínez-Martínez, Irene; Morena-Barrio, María Eugenia de la; Vicente, Vicente; Corral, Javier; MedicinaBackground & Aims: Coagulopathy caused by an imbalance of hemostatic factors is associated with the pathophysiology of liver disease. We have investigated the role of antithrombin (AT), a key anticoagulant serpin, in the onset of liver disease. Methods: Liver injury was induced by CCl4 injection and bile duct ligation (BDL) in wild type (WT) and AT-deficient (AT+/ ) mice. Twenty-four hours after CCl4 treatment, aspartate-transaminase, alanine-transaminase, liver lesion size, leukocyte infiltration, and apoptosis were reduced in WT animals compared to AT+/ mice. Results: Administration of exogenous AT in AT+/ animals did not restore the values observed in WT mice, suggesting that intrahepatic AT might also offer protection against CCl4. In the BDL model, increased liver injury was also evident in AT+/ compared to WT mice. An 85 kDa covalent complex involving AT was identified in immunoblottings of liver lysates from CCl4-treated animals. This complex was also present in anoikis hepatocytes and H2O2-treated HepG2 cells, suggesting a role for AT in apoptosis. Expression of recombinant WT–AT by HEK-EBNA cells increased cell survival while expression of AT mutants, DR393 and R47C, did not modify viability. Finally, plasma anti-FXa activity was attenuated by liver injury, with AT+/ animals showing a greater reduction than WT mice. Conclusions: Our study reveals a protective role of AT against liver injury due to its recognized anticoagulant and antiinflammatory action. AT may also act via a previously unrecognized antiapoptotic effect. The clinical implications of AT deficiency in patients with liver disease should be further addressed. 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
- PublicationEmbargoRole of polymorphonuclear neutrophils (PMNs) and NK cells in the protection conferred by different vaccines against Chlamydophila abortus infection(Elsevier, 2007-06) Ortega, M.; Caro, M. R.; Buendía, A. J.; Gallego, M. C.; Río, L. del; Martínez Cáceres, Carlos Manuel; Nicolás, L.; Cuello, F.; Salinas, J.; Anatomía y Anatomía Patológica ComparadaOvine enzootic abortion (OEA) is caused by Chlamydophila abortus, an intracellular bacterium which acts by infecting the placenta, causing abortion in the last term of gestation. The main prevention strategy against OEA is the vaccination of flocks. An effective vaccine against C. abortus must induce a Th1-like specific immune response, which is characterized by the early production of IFN-γ and the activation of CD8+T cells. Moreover, vaccine effectiveness could be modulated by the functioning of the innate immunity. The purpose of this study was to ascertain how polymorphonuclear neutrophils (PMNs) and NK cells might influence vaccine-induced protection. The live attenuated 1B vaccine and two inactivated experimental vaccines, adjuvated with aluminium hydroxide (AH) or QS-21 (QS), were used in PMN-depleted or NK cell-depleted mice. For PMN depletion, RB6-8C5 monoclonal antibody, which recognizes GR1+receptors (Robben, P.M., LaRegina, M., Kuziel, W.A., Sibley, L.D. 2005. Recruitment of Gr-1+ monocytes is essential for control of acute toxoplasmosis. The Journal of Experimental Medicine 201, 1761–1769.) was used, while for NK cell-depletion the anti-asialo GM1 polyclonal antibody was used. The depletion of PMNs caused 100% mortality in non-vaccinated mice (NV) and 60% mortality in the AH-vaccinated mice by day 10 p.i., while both groups showed a significant increase in their bacterial burden in the liver by day 4 p.i. The depletion of NK cells caused mortality only in the NV group (50% by day 10 p.i.), although this group and the 1B vaccinated mice showed an increased bacterial burden in the liver at day 4 p.i. Our results suggest that the importance of PMNs in inactivated vaccines depends on the adjuvant chosen. The results also demonstrated that the importance of NK cells is greater in live vaccines than in inactivated vaccines.
- PublicationOpen AccessRoles of TGF-beta 1 signaling in the development of osteoarthritis(Universidad de Murcia. Departamento de Biología Celular e Histología, 2016) Fang, Jie; Xu, Lin; Li, Yefu; Zhao, ZhiheOsteoarthritis (OA) is a degenerative joint disorder characterized by the destruction of articular cartilage, subchondral bone and other joint tissues. Although multiple growth factors and cytokines have been shown to be involved in articular cartilage degeneration and subchondral bone destruction, which eventually leads to OA, the molecular mechanisms underlying the pathogenesis of OA are largely unknown. The canonical transforming growth factor beta 1 (TGFβ1) signaling functions as one of the key factors in cartilage and bone formation, remodeling, and maintenance. However, the effects of TGF-β1 signaling on the development of OA are unclear. Numerous studies provide evidence that TGF-β1 is required for the formation of articular cartilage at early stages of joint development. In contrast, other investigations indicate that TGF-β1 may, in fact, be a factor in joint destruction. Therefore, we, in this review article, discuss the “conflicting” roles of TGF-β1 signaling in the development of OA.