Nerve growth factor exacerbates allergic lung inflammation and airway remodeling in a rat model of chronic asthma.
Nerve growth factor (NGF) is critical in the pathogenesis of allergic airway inflammationin vivoand induces proliferation of airway smooth muscle cells and matrix metalloproteinase-9 (MMP-9) expressionin vitro. However, the effects of NGF on chronic pulmonary diseases of allergic origin remain unknown. To investigate the effects of NGF on lung inflammation and airway remodeling, 32 Wistar rats were randomly divided into four groups: control, NGF, ovalbumin (OVA) and anti-rat-β-NGF antibody (anti-NGF). Aerosolized OVA was administered to the rats in the NGF, OVA and anti-NGF groups to generate the asthmatic rat model, and NGF or anti-NGF was administered 3 h prior to OVA inhalation every two days. On day 70, bronchial responsiveness tests, bronchoalveolar lavage (BAL) and cell counting were conducted. The levels of serum OVA-specific immunoglobulin E (IgE) and of T-helper cell type-2 (Th2) cytokines [interleukin (IL)-4 and IL-13] in the BAL fluid were measured by enzyme-linked immunosorbent assay. The expression levels of NGF protein and MMP-9 mRNA, and the activity of MMP-9 in the lungs were detected by western blot analysis, quantitative polymerase chain reaction and gelatin zymography analysis, respectively. Our results showed that NGF significantly increased eosinophilic airway inflammation, persistent airway hyperresponsiveness (AHR), the serum levels of OVA-specific IgE and the levels of Th2 cytokines in the BAL fluid, and also increased the expression levels and activity of MMP-9. However, anti-NGF treatment significantly inhibited eosinophilic airway inflammation, persistent AHR and airway remodeling. The results showed that NGF may have exacerbated the development of airway inflammation, AHR and airway remodeling through a Th2 pathway and by increasing the level of MMP-9 expression. Therefore, anti-NGF is potentially beneficial for preventing and treating patients with asthma.
Department of Pediatric Pulmonology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 100004, P.R. China.
Yun-Gang
YG
Yang
Wei-Min
WM
Tian
Han
H
Zhang
Miao
M
Li
Yun-Xiao
YX
Shang
T-helper cell type-2 cytokines; airway remodeling; asthma; matrix metalloproteinase-9; nerve growth factor