THAYSE REGINA BRUGGEMANN
Projetos de Pesquisa
Unidades Organizacionais
LIM/20 - Laboratório de Terapêutica Experimental, Hospital das Clínicas, Faculdade de Medicina
8 resultados
Resultados de Busca
Agora exibindo 1 - 8 de 8
- Exercise Reduces Lung Fibrosis Involving Serotonin/Akt Signaling(2016) PEREIRA, Paulo Rogerio; OLIVEIRA-JUNIOR, Manoel Carneiro; MACKENZIE, Breanne; CHIOVATTO, Jaime Eduardo Davino; MATOS, Yves; GREIFFO, Flavia Regina; RIGONATO-OLIVEIRA, Nicole Cristine; BRUGEMMAN, Thayse Regina; DELLE, Humberto; IDZKO, Marco; ALBERTINI, Regiane; OLIVEIRA, Ana Paula Ligeiro; DAMACENO-RODRIGUES, Nilsa Regina; CALDINI, Elia Garcia; FERNANDEZ, Isis Ensil; CASTRO-FARIA-NETO, Hugo Caire; DOLHNIKOFF, Marisa; EICKELBERG, Oliver; VIEIRA, Rodolfo PaulaPurpose: Idiopathic pulmonary fibrosis (IPF) is a chronic fibrosing interstitial pneumonia, which involves aberrant serotonin (5-hydroxytryptamine [5-HT]) and Akt signaling. As protective effects of chronic aerobic training (AT) have been demonstrated in the context of lung injury, this study investigated whether AT attenuates bleomycin-induced lung fibrosis partly via a reduction of 5-HT and AKT signaling. Methods: Seventy-two C57BL/6 male mice were distributed in Control (Co), Exercise (Ex), Fibrosis (Fi), and Fibrosis + Exercise (Fi + Ex) groups. Bleomycin (1.5 UI.kg(-1)) was administered on day 1 and treadmill AT began on day 15 and continued for 60 min.d(-1), 5 d.wk(-1) for 4 wk. We evaluated total and differential cell counts in bronchoalveolar lavage (BAL), interleukin (IL)-1A, IL-6, CXCL1/KC, IL-10, tumor necrosis factor alpha, and transforming growth factor A levels in BAL, collagen content in lung parenchyma, 5-HT levels in BAL fluid and in serum, the expression of 5-HT2B receptor, and Akt phosphorylation in lung tissue. Results: AT reduced bleomycin-increased number of total cells (P < 0.001), neutrophils (P < 0.01), macrophages (P < 0.01), and lymphocytes (P < 0.05) in BAL. It also reduced the levels of IL-1A (P < 0.01), IL-6 (P < 0.05), CXCL1/KC (P < 0.001), tumor necrosis factor > (P < 0.001), and transforming growth factor A (P < 0.001). It increased expression of ant-inflammatory cytokine IL-10 (P < 0.001). It reduced bleomycin-increased 5-HT levels in BAL (P < 0.001) and in serum (P < 0.05). Reductions in collagen fiber deposition (P < 0.01), 5-HT2B receptor expression (P < 0.01), and Akt phosphorylation in lung tissue were observed. Conclusions: AT accelerates the resolution of lung inflammation and fibrosis in a model of bleomycin-induced lung fibrosis partly via attenuation of 5-HT/Akt signaling.
- Effects of Swimming on the Inflammatory and Redox Response in a Model of Allergic Asthma(2015) BRUEGGEMANN, T. R.; AVILA, L. C. M.; FORTKAMP, B.; GREIFFO, F. R.; BOBINSKI, F.; MAZZARDO-MARTINS, L.; MARTINS, D. F.; DUARTE, M. M. M. F.; DAFRE, A.; SANTOS, A. R. S.; SILVA, M. D.; SOUZA, L. F.; VIEIRA, R. P.; HIZUME-KUNZLER, D. C.In this study we hypothesized that swimming during sensitization phase could result in a preventive effect in mice with allergic asthma. Swiss mice were divided into 4 groups: Control and Swimming (non-sensitized), OVA and OVA+Swimming (sensitized). The allergic inflammation was induced by 2 intraperitoneal injections and 4 aerosol challenges using ovalbumin. Swimming sessions were performed at high intensity over 3 weeks. 48h after the last challenge mice were euthanized. Swimming decreased OVA-increased total IgE, IL-1, IL-4, IL-5 and IL-6 levels, as well as the number of total cells, lymphocytes and eosinophils in bronchoalveolar lavage fluid, (p<0.05). Simultaneously, swimming also increased IL-10 and glutathione levels in the Swimming and OVA+Swimming groups (p<0.05). The levels of glutathione peroxidase and catalase were increased only in the Swimming group when compared to all groups (p<0.05). 21 days of swimming resulted in an attenuation of pulmonary allergic inflammation followed by an increase of glutathione levels in the OVA group. Swimming only increased the levels of glutathione peroxidase and catalase in non-sensitized mice (p<0.05). These data suggest that the pulmonary anti-inflammatory effects produced by 3 weeks of high-intensity swimming in this model of OVA-induced asthma may be, at least partly, modulated by reduced oxidative stress and increased IL-10 production.
- A plant proteinase inhibitor from Enterolobium contortisiliquum attenuates airway hyperresponsiveness, inflammation and remodeling in a mouse model of asthma(2019) RODRIGUES, Adriana Palmeira Dias; BORTOLOZZO, Anelize Sartori Santos; ARANTES-COSTA, Fernanda Magalhaes; SARAIVA-ROMANHOLO, Beatriz Mangueira; SOUZA, Flavia Castro Ribas de; BRUGGEMANNI, Thayse Regina; SANTANA, Fernanda Paula Roncon; BRITO, Marlon Vilela de; BONTURI, Camila Ramalho; NUNES, Natalia Neto dos Santos; PRADO, Carla Maximo; LEICK, Edna Aparecida; OLIVA, Maria Luiza Vilela; MARTINS, Milton de Arruda; RIGHETTI, Renato Fraga; TIBERIO, Iolanda de Fatima Lopes CalvoIntroduction. Proteinase inhibitors have been associated with anti-inflammatory and antioxidant activities and may represent a potential therapeutic treatment for asthma. Purpose. The aim of the present study was to evaluate the effects of Enterolobium contortisiliquum trypsin inhibitor (EcTI) on pulmonary mechanical function, eosinophilic recruitment, inflammatory cytokines, remodeling and oxidative stress in an experimental model of chronic allergic pulmonary inflammation. Methods. BALB/c mice were divided into 4 groups: C (saline i.p and inhalations with saline), OVA (ovalbumin i.p and inhalations with ovalbumin); C+EC (saline i.p, inhalations with s aline and treatment with EcTI); OVA+EC (ovalbumin i.p, inhalations with ovalbumin and treatment with EcTI). On day 29, we performed the following tests: resistance (Rrs) and elastance (Ers) of the respiratory system; (b) quantify eosinophils, 8-ISO-PGF2 alpha, collagen and elastic fiber volume fractions; (c) IFN-gamma, IL-4, IL-5, IL-13, MMP-9, TIMP-1,TGF-beta, iNOS and p65-NF kappa B-positive cells in the airway and alveolar walls. Results. In OVA+EC group, there was an attenuation of the Rrs and Ers, reduction of eosinophils, IL-4, IL-5, IL-13, IFN-gamma, iNOS and p65-NF kappa B-positive cells compared to OVA group. The 8-ISO-PGF2 alpha, elastic and collagen fibers volume fractions as well as the positive cells for MMP-9, TIMP-1 and TGF-beta positive cells were decreased in OVA+EC compared to the OVA group. Conclusion. EcTI attenuates bronchial hyperresponsiveness, inflammation, remodeling and oxidative stress activation in this experimental mouse model of asthma.
- The Plant Proteinase Inhibitor CrataBL Plays a Role in Controlling Asthma Response in Mice(2018) BORTOLOZZO, Anelize Sartori Santos; RODRIGUES, Adriana Palmeira Dias; ARANTES-COSTA, Fernanda Magalhaes; SARAIVA-ROMANHOLO, Beatriz Mangueira; SOUZA, Flavia Castro Ribas de; BRUGGEMANN, Thayse Regina; BRITO, Marlon Vilela de; FERREIRA, Rodrigo da Silva; CORREIA, Maria Tereza dos Santos; PAIVA, Patricia Maria Guedes; PRADO, Carla Maximo; LEICK, Edna Aparecida; OLIVA, Maria Luiza Vilela; MARTINS, Milton de Arruda; RUIZ-SCHUTZ, Viviane Christina; RIGHETTI, Renato Fraga; TIBERIO, Iolanda de Fatima Lopes CalvoBackground. CrataBL is a protein isolated from Crataeva tapia bark. It has been shown to exhibit several biological properties, including anti-inflammatory, analgesic, antitumor, and insecticidal activities. There are no studies evaluating the role of CrataBL in experimental asthma models. Aim. To evaluate the effects of CrataBL on lung mechanics, inflammation, remodeling, and oxidative stress activation of mice with allergic pulmonary inflammation. Materials and Methods. BALB/c mice (6-7 weeks old, 25-30g) were divided into four groups: nonsensitized and nontreated mice (C group, n=8); ovalbumin- (OVA-) sensitized and nontreated mice (OVA group, n=8); nonsensitized and CrataBL-treated mice (C+CR group, n=8); OVA-sensitized and CrataBL-treated mice (OVA+CR group, n=8). We evaluated hyperresponsiveness to methacholine, bronchoalveolar lavage fluid (BALF), pulmonary inflammation, extracellular matrix remodeling, and oxidative stress markers. Results. CrataBL treatment in OVA- sensitized mice (OVA+CR group) attenuated the following variables compared to OVA- sensitized mice without treatment (OVA group) (all p<0.05): (1) respiratory system resistance (Rrs) and elastance (Ers) after methacholine challenge; (2) total cells, macrophages, polymorphonuclear cells, and lymphocytes in BALF; (3) eosinophils and volume fraction of collagen and elastic fibers in the airway and alveolar wall according to histopathological and morphometry analysis; (4) IL-4-, IL-5-, IL-13-, IL-17-, IFN-gamma-, MMP-9-, TIMP-1-, TGF-beta-, iNOS-, and NF-kB-positive cells and volume of 8-iso-PGF2 in airway and alveolar septa according to immunohistochemistry; and (5) IL-4, IL-5, and IFN-according to an ELISA. Conclusion. CrataBL contributes to the control of hyperresponsiveness, pulmonary inflammation, extracellular matrix remodeling, and oxidative stress responses in an animal model of chronic allergic pulmonary inflammation.
- Cigarette Smoke Increases CD8 alpha(+) Dendritic Cells in an Ovalbumin-Induced Airway Inflammation(2017) BRUGGEMANN, Thayse Regina; FERNANDES, Paula; OLIVEIRA, Luana de Mendonca; SATO, Maria Notomi; MARTINS, Milton de Arruda; ARANTES-COSTA, Fernanda MagalhaesAsthma is an allergic lung disease and, when associated to cigarette smoke exposition, some patients show controversial signs about lung function and other inflammatory mediators. Epidemiologic and experimental studies have shown both increasing and decreasing inflammation in lungs of subjects with asthma and exposed to cigarette smoke. Therefore, in this study, we analyzed how cigarette smoke affects pro-inflammatory and anti-inflammatory mediators in a murine model of allergic pulmonary inflammation. We sensitized Balb/c mice to ovalbumin (OVA) with two intraperitoneal injections. After sensitization, the animals were exposed to cigarette smoke twice a day, 30 min per exposition, for 12 consecutive days. In order to drive the cell to the lungs, four aerosol challenges were performed every 48 h with the same allergen of sensitization. OVA sensitization and challenge developed pulmonary Th2 characteristic response with increased airway responsiveness, remodeling, increased levels of IgE, interleukin (IL)-4, and IL-13. Cigarette smoke, unexpectedly, reduced the levels of IL-4 and IL-13 and simultaneously decreased anti-inflammatory cytokines as IL-10 and transforming growth factor (TGF)-alpha in sensitized and challenged animals. OVA combined with cigarette smoke exposition decreased the number of eosinophils in bronchoalveolar lavage and increased the number of neutrophils in lung. The combination of cigarette smoke and lung allergy increased recruitment of lymphoid dendritic cells (DCs) into lymph nodes, which may be the leading cause to an increase in number and activation of CD8(+) T cells in lungs. In addition, lung allergy and cigarette smoke exposure decreased an important regulatory subtype of DC such as plasmacytoid DC as well as its activation by expression of CD86, PDL2, and ICOSL, and it was sufficient to decrease T regs influx and anti-inflammatory cytokines release such as IL-10 and TGF-alpha but not enough to diminish the structural changes. In conclusion, we observed, in this model, that OVA sensitization and challenge combined with cigarette smoke exposure leads to mischaracterization of the Th2 response of asthma by decreasing the number of eosinophils, IL-4, and IL-13 and increasing number of neutrophils, which is related to the increased number of CD8 alpha(+) DCs and CD8+ T cells as well as reduction of the regulatory cells and its released cytokines.
- Effects of High-Intensity Swimming on Lung Inflammation and Oxidative Stress in a Murine Model of DEP-Induced Injury(2015) AVILA, Leonardo C. M.; BRUGGEMANN, Thayse R.; BOBINSKI, Franciane; SILVA, Morgana Duarte da; OLIVEIRA, Regiane Carvalho; MARTINS, Daniel Fernandes; MAZZARDO-MARTINS, Leidiane; DUARTE, Marta Maria Medeiros Frescura; SOUZA, Luiz Felipe de; DAFRE, Alcir; VIEIRA, Rodolfo de Paula; SANTOS, Adair Roberto Soares; BONORINO, Kelly Cattelan; KUNZLER, Deborah de C. HizumeStudies have reported that exposure to diesel exhaust particles (DEPs) induces lung inflammation and increases oxidative stress, and both effects are susceptible to changes via regular aerobic exercise in rehabilitation programs. However, the effects of exercise on lungs exposed to DEP after the cessation of exercise are not clear. Therefore, the aim of this study was to evaluate the effects of high-intensity swimming on lung inflammation and oxidative stress in mice exposed to DEP concomitantly and after exercise cessation. Male Swiss mice were divided into 4 groups: Control (n = 12), Swimming (30 min/day) (n = 8), DEP (3 mg/mL-10 mu L/mouse) (n = 9) and DEP+Swimming (n = 8). The high-intensity swimming was characterized by an increase in blood lactate levels greater than 1 mmoL/L between 10th and 30th minutes of exercise. Twenty-four hours after the final exposure to DEP, the anesthetized mice were euthanized, and we counted the number of total and differential inflammatory cells in the bronchoalveolar fluid (BALF), measured the lung homogenate levels of IL-1 beta, TNF-alpha, IL-6, INF-(sic), IL-10, and IL-1ra using ELISA, and measured the levels of glutathione, non-protein thiols (GSH-t and NPSH) and the antioxidant enzymes catalase and glutathione peroxidase (GPx) in the lung. Swimming sessions decreased the number of total cells (p<0.001), neutrophils and lymphocytes (p<0.001; p<0.05) in the BALF, as well as lung levels of IL-1 beta (p = 0.002), TNF-alpha (p = 0.003), IL-6 (p = 0.0001) and IFN-(sic) (p = 0.0001). However, the levels of IL-10 (p = 0.01) and IL-1ra (p = 0.0002) increased in the swimming groups compared with the control groups, as did the CAT lung levels (p = 0.0001). Simultaneously, swimming resulted in an increase in the GSH-t and NPSH lung levels in the DEP group (p = 0.0001 and p<0.002). We concluded that in this experimental model, the high-intensity swimming sessions decreased the lung inflammation and oxidative stress status during DEP-induced lung inflammation in mice.
- Sensitization by subcutaneous route is superior to intraperitoneal route in induction of asthma by house dust mite in a murine mode(2015) AUN, Marcelo Vivolo; SARAIVA-ROMANHOLO, Beatriz Mangueira; ALMEIDA, Francine Maria de; BRüGGEMANN, Thayse Regina; KALIL, Jorge; MARTINS, Milton de Arruda; ARANTES-COSTA, Fernanda Magalhães; GIAVINA-BIANCHI, PedroABSTRACT Objective To develop a new experimental model of chronic allergic pulmonary disease induced by house dust mite, with marked production of specific immunoglobulin E (IgE), eosinophilic inflammatory infiltrate in the airways and remodeling, comparing two different routes of sensitization. Methods The protocol lasted 30 days. BALB/c mice were divided into six groups and were sensitized subcutaneously or intraperitoneally with saline (negative control), Dermatophagoides pteronyssinus (Der p) 50 or 500mcg in three injections. Subsequently they underwent intranasal challenge with Der p or saline for 7 days and were sacrificed 24 hours after the last challenge. We evaluated the titration of specific IgE anti-Der p, eosinophilic density in peribronchovascular space and airway remodeling. Results Both animals sensitized intraperitoneally and subcutaneously produced specific IgE anti-Der p. Peribronchovascular eosinophilia increased only in mice receiving lower doses of Der p. However, only the group sensitized with Der p 50mcg through subcutaneously route showed significant airway remodeling. Conclusion In this murine model of asthma, both pathways of sensitization led to the production of specific IgE and eosinophilia in the airways. However, only the subcutaneously route was able to induce remodeling. Furthermore, lower doses of Der p used in sensitization were better than higher ones, suggesting immune tolerance. Further studies are required to evaluate the efficacy of this model in the development of bronchial hyperresponsiveness, but it can already be replicated in experiments to create new therapeutic drugs or immunotherapeutic strategies.
- Aerobic Exercise Decreases Lung Inflammation by IgE Decrement in an OVA Mice Model(2017) HIZUME-KUNZLER, Deborah Camargo; GREIFFO, Flavia R.; FORTKAMP, Barbara; FREITAS, Gabriel Ribeiro; NASCIMENTO, Juliana Keller; BRUGGEMANN, Thayse Regina; AVILA, Leonardo Melo; PERINI, Adenir; BOBINSKI, Franciane; SILVA, Morgana Duarte; LAPA, Fernanda Rocha; VIEIRA, Rodolfo Paula; HOREWICZ, Veronica Vargas; SANTOS, Adair Roberto Soares dos; BONORINO, Kelly CattelanAerobic exercise (AE) reduces lung function decline and risk of exacerbations in asthmatic patients. However, the inflammatory lung response involved in exercise during the sensitization remains unclear. Therefore, we evaluated the effects of exercise for 2 weeks in an experimental model of sensitization and single ovalbumin-challenge. Mice were divided into 4 groups: mice non-sensitized and not submitted to exercise (Sedentary, n = 10); mice non-sensitized and submitted to exercise (Exercise, n = 10); mice sensitized and exposed to ovalbumin (OVA, n = 10); and mice sensitized, submitted to exercise and exposed to OVA (OVA + Exercise, n = 10). 24 h after the OVA/saline exposure, we counted inflammatory cells from bronchoalveolar fluid (BALF), lung levels of total IgE, IL-4, IL-5, IL-10 and IL-1ra, measurements of OVA-specific IgG1 and IgE, and VEGF and NOS-2 expression via western blotting. AE reduced cell counts from BALF in the OVA group (p < 0.05), total IgE, IL-4 and IL-5 lung levels and OVA-specific IgE and IgG1 titers (p < 0.05). There was an increase of NOS-2 expression, IL-10 and IL-1ra lung levels in the OVA groups (p < 0.05). Our results showed that AE attenuated the acute lung inflammation, suggesting immunomodulatory properties on the sensitization process in the early phases of antigen presentation in asthma.