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The effects of cholinergic deficiency induced by reduction in VAChT in pulmonary inflammation induced by cigarrete smoke

Grant number: 16/09353-1
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): November 01, 2016
Effective date (End): October 31, 2017
Field of knowledge:Biological Sciences - Morphology
Principal Investigator:Carla Máximo Prado
Grantee:Emerson Batista da Silva
Home Institution: Instituto de Saúde e Sociedade (ISS). Universidade Federal de São Paulo (UNIFESP). Campus Baixada Santista. Santos , SP, Brazil

Abstract

The dependence of the smoke can result in serious lung damage, leading to the development of diseases such as emphysema, which is considered an abnormality pathological associated with Chronic Obstructive Pulmonary Disease (COPD), which results in an abnormal, permanent enlargement of spaces distal air to the terminal bronchioles, accompanied by destruction of their walls and progressively limitation in the lung airflow. The anti-inflammatory cholinergic system has been extensively studied as a therapeutic target in many diseases, including as an important mediator in the control of lung homeostasis. However, its effect on pulmonary emphysema pathophysiology has been few studied. The aim of the present project will be investigate whether the VAChT reduction interferes with pulmonary emphysema induced by exposure to cigarette smoke. Therefore, animals genetically modified to lower expression of VAChT will be used and we will analyze pulmonary function, inflammatory response and tissue destruction of the lung parenchyma, pro-inflammatory cytokines such as IL-6, IL-8 and IL-17 by ELISA. We expect that the inflammatory response will be increased in the lungs of animals exposed to smoke because the reduction of the cholinergic anti-inflammatory pathway, or that the lung inflammation is reduced since cigarette smoke contains nicotine that stimulates this pathway.