PMID- 24223654 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220316 IS - 1792-0981 (Print) IS - 1792-1015 (Electronic) IS - 1792-0981 (Linking) VI - 6 IP - 5 DP - 2013 Nov TI - Nerve growth factor exacerbates allergic lung inflammation and airway remodeling in a rat model of chronic asthma. PG - 1251-1258 AB - Nerve growth factor (NGF) is critical in the pathogenesis of allergic airway inflammation in vivo and induces proliferation of airway smooth muscle cells and matrix metalloproteinase-9 (MMP-9) expression in 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-beta-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. FAU - Yang, Yun-Gang AU - Yang YG AD - Department of Pediatric Pulmonology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 100004, P.R. China. FAU - Tian, Wei-Min AU - Tian WM FAU - Zhang, Han AU - Zhang H FAU - Li, Miao AU - Li M FAU - Shang, Yun-Xiao AU - Shang YX LA - eng PT - Journal Article DEP - 20130902 PL - Greece TA - Exp Ther Med JT - Experimental and therapeutic medicine JID - 101531947 PMC - PMC3820700 OTO - NOTNLM OT - T-helper cell type-2 cytokines OT - airway remodeling OT - asthma OT - matrix metalloproteinase-9 OT - nerve growth factor EDAT- 2013/11/14 06:00 MHDA- 2013/11/14 06:01 PMCR- 2013/09/02 CRDT- 2013/11/14 06:00 PHST- 2013/04/20 00:00 [received] PHST- 2013/08/20 00:00 [accepted] PHST- 2013/11/14 06:00 [entrez] PHST- 2013/11/14 06:00 [pubmed] PHST- 2013/11/14 06:01 [medline] PHST- 2013/09/02 00:00 [pmc-release] AID - etm-06-05-1251 [pii] AID - 10.3892/etm.2013.1284 [doi] PST - ppublish SO - Exp Ther Med. 2013 Nov;6(5):1251-1258. doi: 10.3892/etm.2013.1284. Epub 2013 Sep 2.