The central glial cell line-derived neurotrophic factor (GDNF) regulates pulmonary function in asthmatic rats

Abstract

Background Asthma is a common chronic inflammatory disease of the airway, but the mechanism is still not fully understood. This study aimed to investigate the effect of glial cell line-derived neurotrophic factor (GDNF) on asthma attacks. Methods An asthmatic rat model was established. GDNF expression in the airway and brain was observed by immunohistochemistry (IHC), and the concentration of GDNF in bronchoalveolar lavage fluid (BALF) was detected by enzyme-linked immunosorbent assay (ELISA). After injection of GDNF and its antibody into the lateral ventricle of asthmatic rats, the pulmonary function was recorded, and the levels of interferon-γ (IFN-γ) and interleukin-4 (IL-4) in BALF were tested. Results GDNF expressions were increased significantly in the lung tissues of asthmatic rats. In the central nervous system (CNS), GDNF-positive immunoreactive substances were observed in multiple brain regions, including the medial amygdala (MeA), paraventricular nucleus (PVN), cortex, and nucleus of solitary tract (NTS). After injection of GDNF into the lateral ventricles of asthmatic rats, the symptoms of asthma and airway inflammation were significantly aggravated, which could be improved by injection of GDNF antibody into the lateral ventricles. Conclusions GDNF expression is increased in the lung and brain in asthmatic rats. During an asthma attack, the increased GDNF expressions in the rat brain remarkably aggravate the asthmatic symptoms.

Anti-inflammatory effects of oral prednisolone at stable state in people treated with mepolizumab: a proteomic and bulk transcriptomics analysis

“…In vitro , GDNF expression is increased in human airway smooth muscle cells in asthma and influences intracellular calcium responses 32 . In rat asthma models, GDNF expression was significantly higher than in controls and central sensitisation to GDNF injected in the lateral ventricle led to a significant increase in bronchial IL-4 and Th2 cells, and significant decrease in pulmonary function 33 . GDNF may contribute to smooth muscle hyperreactivity, and we found it was corticosteroid responsive.…”