DANIELA APARECIDA DE BRITO CERVILHA
Projetos de Pesquisa
Unidades Organizacionais
LIM/20 - Laboratório de Terapêutica Experimental, Hospital das Clínicas, Faculdade de Medicina
4 resultados
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Agora exibindo 1 - 4 de 4
- The tick-derived rBmTI-A protease inhibitor attenuates the histological and functional changes induced by cigarette smoke exposure(2018) LOURENCO, Juliana D.; ITO, Juliana T.; CERVILHA, Daniela A. B.; SALES, Davi S.; RIANI, Alyne; SUEHIRO, Camila L.; GENARO, Isabella S.; DURAN, Adriana; PUZER, Luciano; MARTINS, Milton A.; SASAKI, Sergio D.; LOPES, Fernanda D. T. Q. S.Introduction. Smoking is the main risk factor for chronic obstructive pulmonary disease development and cigarette smoke (CS) exposure is considered an important approach to reproduce in rodents this human disease. We have previously shown that in an elastase induced model of emphysema, the administration of a protease inhibitor (rBmTI-A) prevented and attenuated tissue destruction in mice. Thus, in this study we aimed to verify the effects of rBmTI-A administration on the physiopathological mechanisms of CS induced emphysema. Methods. Mice (C57BL/6) were exposed to CS or room air for 12 weeks. In this period, 3 nasal instillations of rBmTI-A inhibitor or its vehicle were performed. After euthanasia, respiratory mechanics were evaluated and lungs removed for analysis of mean linear intercept, volume proportion of collagen and elastic fibers, density of polymorphonuclear cells, macrophages, and density of positive cells for MMP-12, MMP-9, TIMP-1 and gp91phox. Results. The rBmTI-A administration improved tissue elastance, decreased alveolar enlargement and collagen fibers accumulation to control levels and attenuated elastic fibers accumulation in animals exposed to CS. There was an increase of MMP-12, MMP-9 and macrophages in CS groups and the rBmTIA only decreased the number of MMP-12 positive cells. Also, we demonstrated an increase in gp91phox in CS treated group and in TIMP-1 levels in both rBmTI-A treated groups. Conclusion. In summary, the rBmTI-A administration attenuated emphysema development by an increase of gp91phox and TIMP-1, accompanied by a decrease in MMP-12 levels.
- Regulatory T-Cell Distribution within Lung Compartments in COPD(2017) SALES, Davi S.; ITO, Juliana T.; ZANCHETTA, Ivy A.; ANNONI, Raquel; AUN, Marcelo V.; FERRAZ, Luiz Fernando S.; CERVILHA, Daniela A. B.; NEGRI, Elnara; MAUAD, Thais; MARTINS, Milton A.; LOPES, Fernanda D. T. Q. S.The importance of the adaptive immune response, specifically the role of regulatory T (Treg) cells in controlling the obstruction progression in smokers, has been highlighted. To quantify the adaptive immune cells in different lung compartments, we used lung tissues from 21 never-smokers without lung disease, 22 current and/or ex-smokers without lung disease (NOS) and 13 current and/or ex-smokers with chronic obstructive pulmonary disease (COPD) for histological analysis. We observed increased T, B, IL-17 and BAFF(+) cells in small and large airways of COPD individuals; however, in the NOS, we only observed increase in T and IL-17(+) cells only in small airways. A decrease in the density of Treg(+), TGF-beta(+) and IL-10(+) in small and large airways was observed only in COPD individuals. In the lymphoid tissues, Treg, T,B-cells and BAFF(+) cells were also increased in COPD; however, changes in Treg inhibitory associated cytokineswere not observed in this compartment. Therefore, our results suggest that difference in Treg(+) cell distributions in lung compartments and the decrease in TGF-beta(+) and IL-10(+) cells in the airways may lead to the obstruction in smokers.
- The Th17/Treg Cytokine Imbalance in Chronic Obstructive Pulmonary Disease Exacerbation in an Animal Model of Cigarette Smoke Exposure and Lipopolysaccharide Challenge Association(2019) CERVILHA, Daniela A. B.; ITO, Juliana T.; LOURENCO, Juliana D.; OLIVO, Clarice R.; SARAIVA-ROMANHOLO, Beatriz M.; VOLPINI, Rildo A.; OLIVEIRA-JUNIOR, Manoel C.; MAUAD, Thais; MARTINS, Milton A.; TIBERIO, Iolanda F. L. C.; VIEIRA, Rodolfo P.; LOPES, Fernanda D. T. Q. S.We proposed an experimental model to verify the Th17/Treg cytokine imbalance in COPD exacerbation. Forty C57BL/6 mice were exposed to room air or cigarette smoke (CS) (12 +/- 1 cigarettes, twice a day, 30 min/exposure and 5 days/week) and received saline (50 mu l) or lipopolysaccharide (LPS) (1 mg/kg in 50 mu l of saline) intratracheal instillations. We analyzed the mean linear intercept, epithelial thickness and inflammatory profiles of the bronchoalveolar lavage fluid and lungs. We evaluated macrophages, neutrophils, CD4(+) and CD8(+) T cells, Treg cells, and IL-10(+) and IL-17(+) cells, as well as STAT-3, STAT-5, phospho-STAT3 and phospho-STAT5 levels using immunohistochemistry and IL-17, IL-6, IL-10, INF-gamma, CXCL1 and CXCL2 levels using ELISA. The study showed that CS exposure and LPS challenge increased the numbers of neutrophils, macrophages, and CD4(+) and CD8(+) T cells. Simultaneous exposure to CS/LPS intensified this response and lung parenchymal damage. The densities of Tregs and IL-17(+) cells and levels of IL-17 and IL-6 were increased in both LPS groups, while IL-10 level was only increased in the Control/LPS group. The increased numbers of STAT-3, phospho-STAT3, STAT-5 and phospho-STAT5(+) cells corroborated the increased numbers of IL-17(+) and Treg cells. These findings point to simultaneous challenge with CS and LPS exacerbated the inflammatory response and induced diffuse structural changes in the alveolar parenchyma characterized by an increase in Th17 cytokine release. Although the Treg cell differentiation was observed, the lack of IL-10 expression and the decrease in the density of IL10(+) cells observed in the CS/LPS group suggest that a failure to release this cytokine plays a pivotal role in the exacerbated inflammatory response in this proposed model.
- Different microenvironment stimuli results in distinct patterns of macrophages polarization comparing elastase- and cigarette smoke - induced models of emphysema(2017) KOHLER, Julia Benini; CERVILHA, Daniela A. B.; ITO, Juliana T.; MOREIRA, Alyne R.; SANTANA, Fernanda R.; FARIAS, Talita M.; ALONSO-VALE, Maria Isabel C.; PRADO, Carla M.; MARTINS, Milton Arruda; LOPES, Fernanda D. T. Q. S.; FRANCA, Larissa E.