FLAVIA CASTRO RIBAS DE SOUZA
Projetos de Pesquisa
Unidades Organizacionais
LIM/20 - Laboratório de Terapêutica Experimental, Hospital das Clínicas, Faculdade de Medicina
7 resultados
Resultados de Busca
Agora exibindo 1 - 7 de 7
- Anti-IL17 treatment control responses in lung injury induced by elastase(2018) FUKUZAKI, Silvia; GARRIDO, Aurelio C.; RIGHETTI, Renato F.; SANTOS, Tabata M.; CAMARGO, Leandro N.; ARISTOTELES, Luciana R. C. R. B.; SOUZA, Flavia C. R.; SARAIVA-ROMANHOLO, Beatriz M.; LEICK, Edna A.; PRADO, Carla M.; MARTINS, Milton A.; TIBERIO, Iolanda F. L. C.
- Effect of Anti-IL17 Antibody Treatment Alone and in Combination With Rho-Kinase Inhibitor in a Murine Model of Asthma(2018) SANTOS, Tabata M. dos; RIGHETTI, Renato F.; CAMARGO, Leandro do N.; SARAIVA-ROMANHOLO, Beatriz M.; ARISTOTELES, Luciana R. C. R. B.; SOUZA, Flavia C. R. de; FUKUZAKI, Silvia; ALONSO-VALE, Maria I. C.; CRUZ, Maysa M.; PRADO, Carla M.; LEICK, Edna A.; MARTINS, Milton A.; TIBERIO, Iolanda F. L. C.Background: Interleukin-17 (IL-17) and Rho-kinase (ROCK) play an important role in regulating the expression of inflammatory mediators, immune cell recruitment, hyper-responsiveness, tissue remodeling, and oxidative stress. Modulation of IL-17 and ROCK proteins may represent a promising approach for the treatment of this disease. Objective: To study the effects of an anti-IL17 neutralizing antibody and ROCK inhibitor treatments, separately and in combination, in a murine model of chronic allergy-induced lung inflammation. Methods: Sixty-four BALBc mice, were divided into eight groups (n = 8): SAL (saline-instilled); OVA (exposed-ovalbumin); SAL-RHOi (saline and ROCK inhibitor), OVA-RHOi (exposed-ovalbumin and ROCK inhibitor); SAL-anti-IL17 (saline and anti-IL17); OVA-anti-IL1 7 (exposed-ovalbumin and anti-IL1 7); SAL-RHOi-anti-IL17 (saline, ROCK inhibitor and anti-IL17); and OVA-RHOi-anti-IL17 (exposed-ovalbumin, anti-IL17, and ROCK inhibitor). A 28-day protocol of albumin treatment was used for sensitization and induction of pulmonary inflammation. The anti-IL17A neutralizing antibody (7.5 mu g per treatment) was administered by intraperitoneal injection and ROCK inhibitor (Y-27632) intranasally (10 mg/kg), 1 h prior to each ovalbumin challenge (days 22, 24, 26, and 28). Results: Treatment with the anti-IL17 neutralizing antibody and ROCK inhibitor attenuated the percentage of maximal increase of respiratory system resistance and respiratory system elastance after challenge with methacholine and the inflammatory response markers evaluated (CD4(+), CD8(+), ROCK1, ROCK2, IL-4, IL-5, IL-6, IL-10 IL-13, IL-17, TNF-alpha, TGF-beta, NF-kappa B, dendritic cells, iNOS, MMP-9, MMP-12, TIMP-1, FOXP3, isoprostane, biglycan, decorin, fibronectin, collagen fibers content and gene expression of IL-17, VAChT, and arginase) compared to the OVA group (p < 0.05). Treatment with anti-IL17 and the ROCK inhibitor together resulted in potentiation in decreasing the percentage of resistance increase after challenge with methacholine, decreased the number of IL-5 positive cells in the airway, and reduced, IL-5, TGF beta, FOXP3, ROCK1 and ROCK2 positive cells in the alveolar septa compared to the OVA-RHOi and OVA-anti-IL17 groups (p < 0.05). Conclusion: Anti-IL17 treatment alone or in conjunction with the ROCK inhibitor, modulates airway responsiveness, inflammation, tissue remodeling, and oxidative stress in mice with chronic allergic lung inflammation.
- Effects of Anti-IL-17 on Inflammation, Remodeling, and Oxidative Stress in an Experimental Model of Asthma Exacerbated by LPS(2018) CAMARGO, Leandro do Nascimento; RIGHETTI, Renato Fraga; ARISTOTELES, Luciana Ritha de Cassia Rolim Barbosa; SANTOS, Tabata Maruyama dos; SOUZA, Flavia Castro Ribas de; FUKUZAKI, Silvia; CRUZ, Maysa Mariana; ALONSO-VALE, Maria Isabel Cardoso; SARAIVA-ROMANHOLO, Beatriz Mangueira; PRADO, Carla Maximo; MARTINS, Milton de Arruda; LEICK, Aparecida; TIBERIO, Iolanda de Fatima Lopes CalvoInflammation plays a central role in the development of asthma, which is considered an allergic disease with a classic Th2 inflammatory profile. However, cytokine IL-17 has been examined to better understand the pathophysiology of this disease. Severe asthmatic patients experience frequent exacerbations, leading to infection, and subsequently show altered levels of inflammation that are unlikely to be due to the Th2 immune response alone. This study estimates the effects of anti-IL-17 therapy in the pulmonary parenchyma in a murine asthma model exacerbated by LPS. BALB/c mice were sensitized with intraperitoneal ovalbumin and repeatedly exposed to inhalation with ovalbumin, followed by treatment with or without anti-IL-17. Twenty-four hours prior to the end of the 29-day experimental protocol, the two groups received LPS (0.1 mg/ml intratracheal OVA-LPS and OVA-LPS IL-17). We subsequently evaluated bronchoalveolar lavage fluid, performed a lung tissue morphometric analysis, and measured IL-6 gene expression. OVA-LPS-treated animals treated with anti-IL-17 showed decreased pulmonary inflammation, edema, oxidative stress, and extracellular matrix remodeling compared to the non-treated OVA and OVA-LPS groups (p < 0.05). The anti-IL-17 treatment also decreased the numbers of dendritic cells, FOXP3, NF-kappa B, and Rho kinase 1-and 2-positive cells compared to the non-treated OVA and OVA-LPS groups (p < 0.05). In conclusion, these data suggest that inhibition of IL-17 is a promising therapeutic avenue, even in exacerbated asthmatic patients, and significantly contributes to the control of Th1/Th2/Th17 inflammation, chemokine expression, extracellular matrix remodeling, and oxidative stress in a murine experimental asthma model exacerbated by LPS.
- Protective Effects of Anti-IL17 on Acute Lung Injury Induced by LPS in Mice(2018) RIGHETTI, Renato Fraga; SANTOS, Tabata Maruyama dos; CAMARGO, Leandro do Nascimento; ARISTOTELES, Luciana Ritha Cassia Rolim Barbosa; FUKUZAKI, Silvia; SOUZA, Flavia Castro Ribas de; SANTANA, Fernanda Paula Roncon; AGRELA, Marcus Vinicius Rodrigues de; CRUZ, Maysa Mariana; ALONSO-VALE, Maria Isabel Cardoso; GENARO, Isabella Santos; SARAIVA-ROMANHOLO, Beatriz Mangueira; LEICK, Edna Aparecida; MARTINS, Milton de Arruda; PRADO, Carla Maximo; TIBERIO, Iolanda de Fatima Lopes CalvoIntroduction: T helper 17 (Th17) has been implicated in a variety of inflammatory lung and immune system diseases. However, little is known about the expression and biological role of IL-17 in acute lung injury (ALI).We investigated the mechanisms involved in the effect of anti-IL17 in a model of lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. Methods: Mice were pre-treated with anti-IL17, 1h before saline/LPS intratracheal administration alongside non-treated controls and levels of exhaled nitric oxide (eNO), cytokine expression, extracellular matrix remodeling and oxidative stress, as well as immune cell counts in bronchoalveolar lavage fluid (BALF), and respiratory mechanics were assessed in lung tissue. Results: LPS instillation led to an increase in multiple cytokines, proteases, nuclear factor-kappa B, and Forkhead box P3 (FOXP3), eNO and regulators of the actomyosin cytoskeleton, the number of CD4+ and iNOS-positive cells as well as the number of neutrophils and macrophages in BALF, resistance and elastance of the respiratory system, ARG-1 gene expression, collagen fibers, and actin and 8-iso-PGF2 alpha volume fractions. Pre-treatment with anti-IL17 led to a significant reduction in the level of all assessed factors. Conclusions: Anti-IL17 can protect the lungs from the inflammatory effects of LPS-induced ALI, primarily mediated by the reduced expression of cytokines and oxidative stress. This suggests that further studies using anti-IL17 in a treatment regime would be highly worthwhile.
- Specific NFKappaB and Rho-Quinase inhibitors compared to corticosteroid in asthma model in mice(2017) SOUZA, Flavia; CAMARGO, Leandro; RIGHETTI, Renato; ARISTOTELES, Luciana; MARUYAMA, Tabata; FUKUZAKI, Silvia; LEICK, Edna; MARTINS, Milton; PRADO, Carla; TIBERIO, Iolanda; ROMANHOLO, Beatriz
- Effects of anti-IL17 on acute lung injury induced by LPS in mice(2017) RIGHETTI, Renato; SANTOS, Tabata Maruyama dos; CAMARGO, Leandro do Nascimento; ARISTOTELES, Luciana Ritha de Cassia Rolim Barbosa; FUKUZAKI, Silvia; SOUZA, Flavia Castro Ribas de; CRUZ, Maysa Mariana; ALONSO-VALE, Maria Isabel Cardoso; SARAIVA-ROMANHOLO, Beatriz Mangueira; LEICK, Edna Aparecida; MARTINS, Milton de Arruda; PRADO, Carla Maximo; TIBERIO, Iolanda de Fatima Lopes Calvo
- Effects of anti-IL17 on inflammation, remodeling, and oxidative stress in an experimental model of asthma exacerbated by LPS(2018) CAMARGO, Leandro; RIGHETTI, Renato F.; ARISTOTELES, Luciana R. C. R. B.; SANTOS, Tabata M.; SOUZA, Flavia C. R.; FUKUZAKI, Silvia; CRUZ, Maysa M.; ALONSO-VALE, Maria Isabel C.; SARAIVA-ROMANHOLO, Beatriz M.; PRADO, Carla M.; MARTINS, Milton A.; LEICK, Edna A.; TIBERIO, Iolanda F. L. C.