Navegando por Palavras-chave "Distal lung"
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- ItemAcesso aberto (Open Access)Effects of Anti-IL-17 on Inflammation, Remodeling, and Oxidative Stress in an Experimental Model of Asthma Exacerbated by LPS(Frontiers Media Sa, 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 [UNIFESP]; Alonso-Vale, Maria Isabel Cardoso [UNIFESP]; Saraiva-Romanholo, Beatriz Mangueira; Prado, Carla Maximo [UNIFESP]; Martins, Milton de Arruda; Leick, Aparecida; Lopes Calvo Tiberio, Iolanda de Fatima; Universidade Federal de São Paulo (UNIFESP)Inflammation 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.
- ItemSomente MetadadadosEffects of Rho-kinase inhibition in lung tissue with chronic inflammation(Elsevier B.V., 2014-02-01) Righett, Renato Fraga; Silva Pigati, Patricia Angeli da; Possa, Samantha Souza; Habrum, Fabio Cetinic; Xisto, Debora Goncalves; Antunes, Mariana Alves; Leick, Edna Aparecida; Prado, Carla Maximo [UNIFESP]; Martins, Milton de Arruda; Macedo Rocco, Patricia Rieken; Lopes Calvo Tiberio, Iolanda de Fatima; Universidade de São Paulo (USP); Universidade Federal do Rio de Janeiro (UFRJ); Universidade Federal de São Paulo (UNIFESP)We evaluated whether Rho-kinase inhibition (Y-27632) modulated distal lung responsiveness, inflammation, extracellular matrix remodeling and oxidative stress activation in guinea pigs (GPs) with chronic allergic inflammation. GPs were submitted to inhalation of ovalbumin (OVA-2x/week/4 weeks). From the 5th inhalation on, the Rho-kinase inhibitor group animals were submitted to Y-27632 inhalation 10 min before each inhalation of OVA. Seventy-two hours after the seventh inhalation, the oscillatory mechanics of the distal lung strips were assessed under the baseline condition and after the ovalbumin challenge. Subsequently, the lung slices were submitted to morphometry. Rho-kinase inhibition in the ovalbumin-exposed animals attenuated distal lung elastance and resistance, eosinophils, IL-2, IL-4, IL-5, IL-13, TIMP-1, MMP-9, TGF-beta, IFN-gamma, NF-kappa B and iNOS-positive cells and the volume fraction of 8-iso-PGF2 alpha, elastic, collagen and actin in alveolar walls compared with the OVA group (P < 0.05). Rho-kinase inhibition contributed to the control of distal lung responsiveness, eosinophilic and Th1/Th2 responses and extracellular matrix remodeling in an animal model of chronic allergic inflammation. (C) 2014 Elsevier B.V. All rights reserved.