Effects of cholinergic system in acute and chronic pulmonary inflammation

• Grant number: 14/25689-4
• Support Opportunities: Regular Research Grants
• Start date: March 01, 2016
• End date: April 30, 2018
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Carla Máximo Prado
• Grantee: Carla Máximo Prado
• Host Institution: Instituto de Saúde e Sociedade (ISS). Universidade Federal de São Paulo (UNIFESP). Campus Baixada Santista. Santos , SP, Brazil
• Associated researchers: Iolanda de Fátima Lopes Calvo Tibério ; Luciana Chagas Caperuto ; Marco Antonio Maximo Prado ; Milton de Arruda Martins ; Vania Ferreira Prado

Abstract

The anti-inflammatory cholinergic system (SCAI), described a few years ago, has been not fully investigated in the lung and may be an important therapeutic target for the treatment of pulmonary diseases. We recently demonstrated that animals with VAChT deficiency, the protein which transports acetylcholine (ACh), developed inflammation, activation of the NF-kB and reduction of JAK2-STAT3-SOCS3 pathway in lung. The reduction of VAChT also increased lung inflammation in an experimental model of asthma and emphysema. Based on that, several questions have appeared in order to better understand the role of cholinergic anti-inflammatory system in lung and also to evaluate new possible therapeutic targets involved in these diseases. This study aims to advance the understanding of SCAI in chronic and acute pulmonary responses, and make progress on this line of research poorly investigated in lung. Objectives: 1. Evaluate whether the long-term VAChT reduction interfere in the lung inflammation in naïve mice; 2 Evaluate the effect of genetic reduction of VAChT in an experimental model of acute inflammation; 3. Evaluate the effect of nicotinic receptor stimulation in the acute inflammation model; 4. Evaluate the effects of nicotinic receptor stimulation in experimental asthma model; 5 Evaluate whether SCAI is involved in the effects of a flavonoid sakuranetin in attenuating lung inflammation in an experimental asthma model. 6 Evaluate the effects of nicotinic receptor stimulation in experimental emphysema model. For that, VAChT strain mice with reduced cholinergic tone, C57BL and Balb-C mice will be used and lung function, pulmonary histopathology and mechanisms involved in acute lung injury and experimental asthma and lung emphysema models will be evaluated. (AU)

Scientific publications

(10)

(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)

PEDROSO SAKODA, CAMILA PIVARI; DE TOLEDO, ALESSANDRA CHOQUETA; PERINI, ADENIR; PINHEIRO, NATHALIA MONTOURO; HIYANE, MEIRE IOSHIE; GRECCO, SIMONE DOS SANTOS; LOPES CALVO TIBERIO, IOLANDA DE FATIMA; SARAIVA CAMARA, NIELS OLSEN; MARTINS, MILTON DE ARRUDA; GHILARDI LAGO, JOAO HENRIQUE; et al. Sakuranetin reverses vascular peribronchial and lung parenchyma remodeling in a murine model of chronic allergic pulmonary inflammation. ACTA HISTOCHEMICA, v. 118, n. 6, p. 615-624, 2016. (14/25689-4, 10/14831-3)

GAMES, ELLEN; GUERREIRO, MARINA; SANTANA, FERNANDA R.; PINHEIRO, NATHALIA M.; DE OLIVEIRA, EMERSON A.; LOPES, FERNANDA D. T. Q. S.; OLIVO, CLARICE R.; TIBERIO, IOLANDA F. L. C.; MARTINS, MILTON A.; LAGO, JOAO HENRIQUE G.; et al. Structurally Related Monoterpenes p-Cymene, Carvacrol and Thymol Isolated from Essential Oil from Leaves of Lippia sidoides Cham. (Verbenaceae) Protect Mice against Elastase-Induced Emphysema. Molecules, v. 21, n. 10, OCT 2016. (15/11936-2, 14/25689-4, 11/51739-0, 13/02881-4)

SANTANA, FERNANDA P. R.; RICARDO-DA-SILVA, FERNANDA Y.; FANTOZZI, EVELYN T.; PINHEIRO, NATHALIA M.; TIBERIO, IOLANDA F. L. C.; MOREIRA, LUIZ FELIPE PINHO; PRADO, MARCO ANTONIO M.; PRADO, VANIA F.; TAVARES-DE-LIMA, WOTHAN; PRADO, CARLA MAXIMO; et al. Lung Edema and Mortality Induced by Intestinal Ischemia and Reperfusion Is Regulated by VAChT Levels in Female Mice. Inflammation, v. 44, n. 4, p. 1553-1564, AUG 2021. (14/25689-4, 18/06088-0)

SUEHIRO, CAMILA LIYOKO; SOUZA, NATALIA TIEMI SIMOKOMAKI; DA SILVA, EMERSON BATISTA; CRUZ, MAYSA MARIANA; LAIA, ROSEANE MARTINS; SANTOS, STHEFFANY DE OLIVEIRA; SANTANA-NOVELLI, FERNANDA PAULA RONCON; DE CASTRO, THAMYRES BARROS PEREIRA; LOPES, FERNANDA D. T. Q. S.; PINHEIRO, NATHALIA MONTOURO; et al. Aerobic exercise training engages cholinergic signaling to improve emphysema induced by cigarette smoke exposure in mice. Life Sciences, v. 301, p. 9-pg., 2022-05-04. (16/09353-1, 14/25689-4)

SANTANA, FERNANDA P. R.; DA SILVA, RAFAEL C.; GRECCO, SIMONE DOS S.; PINHEIRO, ARUANA J. M. C. R.; CAPERUTO, LUCIANA C.; ARANTES-COSTA, FERNANDA M.; CLAUDIO, SAMUEL R.; YOSHIZAKI, KELLY; MACCHIONE, MARIANGELA; RIBEIRO, DANIEL A.; et al. Inhibition of MAPK and STAT3-SOCS3 by Sakuranetin Attenuated Chronic Allergic Airway Inflammation in Mice. Mediators of Inflammation, v. 2019, SEP 3 2019. (18/06088-0, 14/25689-4)

SANTANA, FERNANDA P. R.; DA SILVA, RAFAEL C.; PONCI, VITOR; PINHEIRO, ARUANA J. M. C. R.; OLIVO, CLARICE R.; CAPERUTO, LUCIANA C.; ARANTES-COSTA, FERNANDA M.; CLAUDIO, SAMUEL R.; RIBEIRO, DANIEL A.; TIBERIO, IOLANDA F. L. C.; et al. Dehydrodieugenol improved lung inflammation in an asthma model by inhibiting the STAT3/SOCS3 and MAPK pathways. Biochemical Pharmacology, v. 180, OCT 2020. (14/25689-4, 18/06088-0)

PINHEIRO, NATHALIA M.; SANTANA, FERNANDA P. R.; ALMEIDA, RAFAEL RIBEIRO; GUERREIRO, MARINA; MARTINS, MILTON A.; CAPERUTO, LUCIANA C.; CAMARA, NIELS O. S.; WENSING, LISLAINE A.; PRADO, VANIA F.; TIBERIO, IOLANDA F. L. C.; et al. Acute lung injury is reduced by the alpha 7nAChR agonist PNU-282987 through changes in the macrophage profile. FASEB JOURNAL, v. 31, n. 1, p. 320-332, JAN 2017. (12/02270-2, 13/02881-4, 14/25689-4)

ISABEL BITTENCOURT-MERNAK, MARCIA; PINHEIRO, NATHALIA M.; SANTANA, FERNANDA P. R.; GUERREIRO, MARINA P.; SARAIVA-ROMANHOLO, BEATRIZ M.; GRECCO, SIMONE S.; CAPERUTO, LUCIANA C.; FELIZARDO, RAPHAEL J. F.; CAMARA, NIELS O. S.; TIBERIO, IOLANDA F. L. C.; et al. Prophylactic and therapeutic treatment with the flavonone sakuranetin ameliorates LPS-induced acute lung injury. AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, v. 312, n. 2, p. L217-L230, FEB 2017. (14/25689-4)

SANTANA, FERNANDA P. R.; PINHEIRO, NATHALIA M.; BITTENCOURT-MERNAK, MARCIA I.; PERINI, ADENIR; YOSHIZAKI, KELLY; MACCHIONE, MARIANGELA; SALDIVA, PAULO H. N.; MARTINS, MILTON A.; TIBERIO, IOLANDA F. L. C.; PRADO, MARCO ANTONIO M.; et al. Vesicular acetylcholine transport deficiency potentiates some inflammatory responses induced by diesel exhaust particles. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY, v. 167, p. 494-504, JAN 15 2019. (14/25689-4, 11/15817-7)

PINHEIRO, NATHALIA M.; MIRANDA, CLAUDIA J. C. P.; SANTANA, FERNANDA R.; BITTENCOURT-MERNAK, MARCIA; ARANTES-COSTA, FERNANDA M.; OLIVO, CLARICE; PERINI, ADENIR; FESTA, SERGIO; CAPERUTO, LUCIANA C.; TIBERIO, IOLANDA F. L. C.; et al. length Effects of VAChT reduction and alpha 7nAChR stimulation by PNU-282987 in lung inflammation in a model of chronic allergic airway inflammation. European Journal of Pharmacology, v. 882, SEP 5 2020. (14/25689-4)