title: Dermatophagoides pteronyssinus 2 regulates nerve growth factor release to induce airway inflammation via a reactive oxygen species-dependent pathway.
abstract: 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.
authors.affiliation: Department of Biotechnology, National Formosa University, Yunlin, Taiwan.
authors.forename: Yi-Ling
authors.initials: YL
authors.lastname: Ye
authors.forename: Hung-Tsung
authors.initials: HT
authors.lastname: Wu
authors.forename: Chiou-Feng
authors.initials: CF
authors.lastname: Lin
authors.forename: Chia-Yuan
authors.initials: CY
authors.lastname: Hsieh
authors.forename: Jiu-Yao
authors.initials: JY
authors.lastname: Wang
authors.forename: Fu-Hua
authors.initials: FH
authors.lastname: Liu
authors.forename: Ching-Ting
authors.initials: CT
authors.lastname: Ma
authors.forename: Chia-Hao
authors.initials: CH
authors.lastname: Bei
authors.forename: Yu-Lun
authors.initials: YL
authors.lastname: Cheng
authors.forename: Ching-Chun
authors.initials: CC
authors.lastname: Chen
authors.forename: Bor-Luen
authors.initials: BL
authors.lastname: Chiang
authors.forename: Chiung-Wen
authors.initials: CW
authors.lastname: Tsao
mesh_terms: D014013:1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt / Q000494:pharmacology; D000485:Allergens / Q000633:toxicity; D000818:Animals; D039741:Antigens, Dermatophagoides / Q000633:toxicity*; D060829:Arthropod Proteins; D001249:Asthma / Q000209:etiology* / Q000503:physiopathology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002460:Cell Line; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000187:drug effects / Q000502:physiology; D005260:Female; D007249:Inflammation / Q000209:etiology / Q000503:physiopathology; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D020932:Nerve Growth Factor / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D000485:Allergens; D039741:Antigens, Dermatophagoides; D060829:Arthropod Proteins; C451163:Dermatophagoides pteronyssinus antigen p 2; D017382:Reactive Oxygen Species; D014013:1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt; D020932:Nerve Growth Factor