The role of cholinergic antiinflammatory pathway in a model of Asthma-COPD Overlap Syndrome (ACOS) modelo experimental

• Grant number: 22/02510-5
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: July 01, 2022
• End date: April 30, 2028
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Iolanda de Fátima Lopes Calvo Tibério
• Grantee: Vitória Caroline de Queiroz
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 18/02537-5 - Characterization of asthma-COPD overlap syndrome (ACOS): experimental and clinical studies, AP.TEM
• Associated scholarship(s): 23/09694-7 - Evaluation of cholinergic receptors in A549 and BEAS-2b cells stimulated with IL13 and neutrophil elastase, BE.EP.DD

Abstract

Asthma and COPD (Chronic Obstructive Pulmonary Disease) are well defined. Recently, ACOS (Asthma Overlap Syndrome and COPD) has been discussed, a variant, with clinical manifestations similar to what is reported in COPD, but with a significant response to the use of bronchodilators. The anti-inflammatory cholinergic system and nicotinic receptors have been shown to be important in modulating pulmonary inflammation. Animals with reduced acetylcholine (ACh) release, due to reduced acetylcholine vesicular transporter (VAChT) present worsening pulmonary inflammation per se, induced by Asthma and atmospheric pollution and the pharmacological stimulation of nicotinic alpha-7 receptors (nAChR±7) can reverse the changes induced by Bronchial Asthma in mice. Thus, our hypothesis is that the anti-inflammatory cholinergic system participates in the development of the inflammatory response in model of ACOS and that the pharmacological stimulation of nAChR±7 could be a future therapeutic strategy. To this end, the objective of this project is to: assess the effects of reducing VAChT and stimulating nAChR±7 in vivo in experimental ACOS model. Animals of the lineage knock-down VAChT (KD-VAChT) will be submitted to the ACOS induction protocol, Asthma model and Pulmonary Emphysema. Part of these animals will be treated with PNU, a nAChR±7 agonist. Lung function and inflammatory response will be assessed, as well as analysis of possible signaling pathways such as JAK-STAT and MAPKinase. The statistical analysis will be performed by multiple comparisons with the Student-Newman-Keuls test. (AU)

Scientific publications

(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)

ALMEIDA, FRANCINE MARIA; OLIVEIRA, ROSELAINE MARIA; QUEIROZ, VITORIA CAROLINE; OLIVO, CLARICE ROSA; SARAIVA-ROMANHOLO, BEATRIZ MANGUEIRA; LOTUFO, PAULO A.; BENSENOR, ISABELA; SANTOS, ITAMAR SOUZA; LOPES CALVO TIBERIO, IOLANDA FATIMA. Pulmonary function evaluation on Asthma-COPD overlap from ELSA-Brasil cohort study.. European Respiratory Journal, v. 62, p. 3-pg., 2023-09-09. (19/26449-0, 22/02510-5, 18/02537-5)