Dermatophagoides pteronyssinus 2 regulates nerve growth factor release to induce airway inflammation via a reactive oxygen species-dependent pathway

Autor: Yi Ling Ye, Chiou Feng Lin, Hung Tsung Wu, Chia Yuan Hsieh, Jiu Yao Wang, Yu Lun Cheng, Fu Hua Liu, Ching Chun Chen, Ching Ting Ma, Bor-Luen Chiang, Chia Hao Bei, Chiung Wen Tsao
Rok vydání: 2011
Předmět:
Zdroj: American Journal of Physiology-Lung Cellular and Molecular Physiology. 300:L216-L224
ISSN: 1522-1504
1040-0605
DOI: 10.1152/ajplung.00165.2010
Popis: Group 2 allergen of Dermatophagoides pteronyssinus 2 (Der p2) induces airway inflammation without protease activity, and elevated nerve growth factor (NGF) levels are also found in this inflammation. How the allergen Der p2 regulates NGF release via reactive oxygen species (ROS) to induce inflammation remains unclear. In the present study, intratracheal administration of Der p2 to mice led to inflammatory cell infiltration, mucus gland hyperplasia, and NGF upregulation in the bronchial epithelium, as well as elevated ROS and NGF production in bronchoalveolar lavage fluids. In addition, Der p2 caused fibrocyte accumulation and mild fibrosis. p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK) inhibitors inhibited Der p2-induced NGF release in LA4 lung epithelial cells and MLg lung fibroblasts. Pretreatment with an antioxidant, tiron, reduced the Der p2-induced ROS production, NGF expression and release, p38 MAPK or JNK phosphorylation, and airway inflammation. These results suggest that Der p2 allergen-induced airway inflammation and elevated NGF release were through increasing ROS production and a MAPK-dependent pathway. The use of an antioxidant, tiron, may provide a new therapeutic modality for the treatment of allergic asthma.
Databáze: OpenAIRE