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Anti-IL-17 in the modulation of lung mechanics, inflammation, oxidative stress, extracellular matrix remodeling in mice with chronic pulmonary inflammation associated or not with acute lung injury induced by LPS acute lung injury by LPS

Grant number: 13/17944-1
Support type:Regular Research Grants
Duration: May 01, 2014 - October 31, 2016
Field of knowledge:Biological Sciences - Physiology
Principal Investigator:Iolanda de Fátima Lopes Calvo Tibério
Grantee:Iolanda de Fátima Lopes Calvo Tibério
Home Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Assoc. researchers:Carla Máximo Prado ; Edna Aparecida Leick ; Flávia Castro Ribas de Souza ; Luciana Ritha de Cássia Rolim Barbosa Aristóteles ; Milton de Arruda Martins ; Patricia Angeli da Silva Pigati ; Renato Fraga Righetti ; Ruth Andriani Baroni ; Samantha Souza Possa

Abstract

Th17 cytokines seem to play an important role in the pathogenesis of chronic allergic pulmonary inflammation and acute lung injury (ALI), although its exact influence is uncertain. Studies have demonstrated an influence of these cytokines in modulating inflammation or infection, and the infection is, in turn, one of the factors involved in the maintenance of the inflammation response in asthma. Many of the effects of this pathway have not been investigated in models of chronic pulmonary inflammation (asthma) associated or not with acute lung injury (ALI). In the present study will evaluate the effects of treatment with anti-IL-17 in a model of chronic allergic pulmonary inflammation and ALI induced by lipopolysaccharide (LPS). We assess lung mechanics, inflammatory response, activation of oxidative stress, extracellular matrix remodeling in the airways and in the distal lung of mice chronically exposed to ovalbumin or lung injury induced by LPS. The BALB/c mice will be sensitized to ovalbumin for 28 days and controls receive saline treatment groups receive one hour prior to exposure to ovalbumin administration of neutralizing antibody anti-IL-17 intranasal and intraperitoneal on days 22, 24, 26 and 28. The animals underwent LPA will be anesthetized with isoflurane and will receive single intratracheal instillation of LPS diluted in saline at a dose of 5mg/kg. The treatment groups will receive a single dose of anti-IL-17 hour before exposure to LPS and control groups receive saline. Twenty-four hours after the end of the experimental protocol, the animals will be subject to an assessment of lung mechanics. Then it will be made histological analyzes for numbers of CD4 +, CD8 +, dendritic cells, collagen deposition (types I, III and V), elastic, actin, decorin, byglican, lumican, fibronectin, integrins (±V²6 and TLR3) , FOXP3, CCL-11, TARC, MMP-9, MMP-12 and TIMP-1, isoprostane, cytokines (IL-2, IL-4, IL-5, IL-6, IL-10, IL-13, IL -17, IFN-gamma, TNF-±, TGF-²1, NFºBand of Rho kinase activityin different groups. (AU)

Scientific publications (5)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
DIAS RODRIGUES, ADRIANA PALMEIRA; SANTOS BORTOLOZZO, ANELIZE SARTORI; ARANTES-COSTA, FERNANDA MAGALHAES; SARAIVA-ROMANHOLO, BEATRIZ MANGUEIRA; RIBAS DE SOUZA, FLAVIA CASTRO; BRUGGEMANNI, THAYSE REGINA; RONCON SANTANA, FERNANDA PAULA; DE BRITO, MARLON VILELA; BONTURI, CAMILA RAMALHO; DOS SANTOS NUNES, NATALIA NETO; PRADO, CARLA MAXIMO; LEICK, EDNA APARECIDA; VILELA OLIVA, MARIA LUIZA; MARTINS, MILTON DE ARRUDA; RIGHETTI, RENATO FRAGA; LOPES CALVO TIBERIO, IOLANDA DE FATIMA. A plant proteinase inhibitor from Enterolobium contortisiliquum attenuates airway hyperresponsiveness, inflammation and remodeling in a mouse model of asthma. HISTOLOGY AND HISTOPATHOLOGY, v. 34, n. 5, p. 537-552, MAY 2019. Web of Science Citations: 0.
RIGHETTI, RENATO FRAGA; DOS SANTOS, TABATA MARUYAMA; CAMARGO, LEANDRO DO NASCIMENTO; ROLIM BARBOSA ARISTOTELES, LUCIANA RITHA CASSIA; FUKUZAKI, SILVIA; RIBAS DE SOUZA, FLAVIA CASTRO; RONCON SANTANA, FERNANDA PAULA; RODRIGUES DE AGRELA, MARCUS VINICIUS; CRUZ, MAYSA MARIANA; CARDOSO ALONSO-VALE, MARIA ISABEL; GENARO, ISABELLA SANTOS; SARAIVA-ROMANHOLO, BEATRIZ MANGUEIRA; LEICK, EDNA APARECIDA; MARTINS, MILTON DE ARRUDA; PRADO, CARLA MAXIMO; LOPES CALVO TIBERIO, IOLANDA DE FATIMA. Protective Effects of Anti-IL17 on Acute Lung Injury Induced by LPS in Mice. FRONTIERS IN PHARMACOLOGY, v. 9, OCT 4 2018. Web of Science Citations: 4.
DOS SANTOS, TABATA M.; RIGHETTI, RENATO F.; CAMARGO, LEANDRO DO N.; SARAIVA-ROMANHOLO, BEATRIZ M.; ARISTOTELES, LUCIANA R. C. R. B.; DE SOUZA, FLAVIA C. R.; FUKUZAKI, SILVIA; ALONSO-VALE, MARIA I. C.; CRUZ, MAYSA M.; PRADO, CARLA M.; LEICK, EDNA A.; 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. FRONTIERS IN PHYSIOLOGY, v. 9, SEP 5 2018. Web of Science Citations: 5.
CAMARGO, LEANDRO DO NASCIMENTO; RIGHETTI, RENATO FRAGA; ROLIM BARBOSA ARISTOTELES, LUCIANA RITHA DE CASSIA; DOS SANTOS, TABATA MARUYAMA; RIBAS DE SOUZA, FLAVIA CASTRO; FUKUZAKI, SILVIA; CRUZ, MAYSA MARIANA; CARDOSO ALONSO-VALE, MARIA ISABEL; MANGUEIRA SARAIVA-ROMANHOLO, BEATRIZ; PRADO, CARLA MAXIMO; MARTINS, MILTON DE ARRUDA; LEICK, APARECIDA; LOPES CALVO TIBERIO, IOLANDA DE FATIMA. Effects of Anti-IL-17 on Inflammation, Remodeling, and Oxidative Stress in an Experimental Model of Asthma Exacerbated by LPS. FRONTIERS IN IMMUNOLOGY, v. 8, JAN 5 2018. Web of Science Citations: 18.
MARTINS-OLIVERA, BRUNO TADEU; ALMEIDA-REIS, RAFAEL; THEODORO-JUNIOR, OSMAR APARECIDO; OLIVA, LEANDRO VILELA; DOS SANTOS NUNES, NATALIA NETO; OLIVO, CLARICE ROSA; DE BRITO, MARLON VILELA; PRADO, CARLA MAXIMO; LEICK, EDNA APARECIDA; MARTINS, MILTON DE ARRUDA; VILELA OLIVA, MARIA LUIZA; RIGHETTI, RENATO FRAGA; LOPES CALVO TIBERIO, IOLANDA DE FATIMA. The Plant-Derived Bauhinia bauhinioides Kallikrein Proteinase Inhibitor (rBbKI) Attenuates Elastase-Induced Emphysema in Mice. Mediators of Inflammation, 2016. Web of Science Citations: 8.

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