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

作者：Ye Yi Ling; Wu Hung Tsung; Lin Chiou Feng; Hsieh Chia Yuan; Wang Jiu Yao; Liu Fu Hua; Ma Ching Ting; Bei Chia Hao; Cheng Yu Lun; Chen Ching Chun; Chiang Bor Luen; Tsao Chiung Wen^*

来源：American Journal of Physiology - Lung Cellular and Molecular Physiology, 2011, 300(2): L216-L224.

DOI：10.1152/ajplung.00165.2010

• mitogen-activated protein kinase
• mite
• antioxidant

Ye Y, Wu H, Lin C, Hsieh C, Wang J, Liu F, Ma C, Bei C, Cheng Y, Chen C, Chiang B, Tsao C. Dermatophagoides pteronyssinus 2 regulates nerve growth factor release to induce airway inflammation via a reactive oxygen species-dependent pathway. Am J Physiol Lung Cell Mol Physiol 300: L216-L224, 2011. First published November 18, 2010; doi:10.1152/ajplung.00165.2010.-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.

• 出版日期2011-2