Abstract
Asthma is a chronic inflammatory disease characterized by eosinophilic and Th2 airway inflammation. The cholinergic anti-inflammatory pathway has been described to control inflammation in several organs including the lung. It links the brain with the immune system through effects of acetylcholine (ACh) particularly on the α7 nicotinic acetylcholine receptor (α7nAChR).
Aim: To investigate whether α7nAChR modulates airway inflammation and remodeling in a model of asthma.
Methods: BALB/c mice previously sensitized to ovalbumin (OVA) (29 day protocol) received three doses of PNU282987 (PNU) (α7nAChR agonist) beginning on the 22nd day until the end of the OVA protocol. The cells in bronchoalveolar lavage fluid (BALF) was evaluated and the PNU (0.5mg.Kg-1) was the most effective dose and was used for the other assays. Therefore, peripheral blood cells, BALF cytokines, and airway remodeling were evaluated.
Results: PNU treatment in OVA-sensitized mice reduced peripheral blood and airways eosinophils (p<0.001); it also reduced inflammatory cells and the levels of IL-4 and IL-13 (p<0.05) in BALF. The treatment with MLA (α7nAChR antagonist) prior to PNU treatment in OVA-sensitized mice prevented the benefic effects of PNU on lung inflammation. Moreover, PNU reduced collagen fibers deposition and the levels of MMP-9 and TIMP-1 around airways compared to OVA (p<0.05).
Conclusion: The α7nAChR stimulation reduced inflammation and remodeling in an experimental model of allergic airway inflammation. These data suggested that α7nAChR may be a new target to be explored in asthma. Supported by FAPESP/CNPq/CAPESP.
- Copyright ©the authors 2016
