title: Role of prostaglandin D2 /CRTH2 pathway on asthma exacerbation induced by Aspergillus fumigatus.
abstract: Aspergillus fumigatus is often associated in asthmatic patients with the exacerbation of asthma symptoms. The pathomechanism of this phenomenon has not been fully understood. Here, we evaluated the immunological mechanisms and the role of the prostaglandin D2 / Chemoattractant Receptor-Homologous Molecule Expressed on Th2 Cells (CRTH2) pathway in the development of Aspergillus-associated asthma exacerbation. We studied the effects of A. fumigatus on airway inflammation and bronchial hyper-responsiveness in a rat model of chronic asthma. Inhalation delivery of A. fumigatus conidia increased the airway eosinophilia and bronchial hyper-responsiveness in ovalbumin-sensitized, challenged rats. These changes were associated with prostaglandin D2 synthesis and CRTH2 expression in the lungs. Direct inflammation occurred in ovalbumin-sensitized, challenged animals, whereas pre-treatment with an antagonist against CRTH2 nearly completely eliminated the A. fumigatus-induced worsening of airway eosinophilia and bronchial hyper-responsiveness. Our data demonstrate that production of prostaglandin D2 followed by eosinophil recruitment into the airways via a CRTH2 receptor are the major pathogenic factors responsible for the A. fumigatus-induced enhancement of airway inflammation and responsiveness.
authors: Department of Respiratory Medicine, Shanghai First People's Hospital Affiliated Shanghai JiaoTong University School of Medicine, Shanghai, China.
authors: Haixia
authors: H
authors: Liu
authors: Mingrui
authors: M
authors: Zheng
authors: Jianou
authors: J
authors: Qiao
authors: Yajie
authors: Y
authors: Dang
authors: Pengyu
authors: P
authors: Zhang
authors: Xianqiao
authors: X
authors: Jin
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001232:Aspergillus fumigatus / Q000472:pathogenicity*; D001249:Asthma / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology / Q000503:physiopathology; D016535:Bronchial Hyperreactivity / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology / Q000503:physiopathology; D004195:Disease Models, Animal; D004804:Eosinophils / Q000276:immunology / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology / Q000503:physiopathology; D008297:Male; D010047:Ovalbumin; D015230:Prostaglandin D2 / Q000378:metabolism*; D055732:Pulmonary Aspergillosis / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology / Q000503:physiopathology; D011657:Pulmonary Eosinophilia / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D051381:Rats; D017208:Rats, Wistar; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D000893:Anti-Inflammatory Agents; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; D010047:Ovalbumin; D015230:Prostaglandin D2; C036293:prostaglandin D2 receptor
keywords: Aspergillus fumigatus; CRTH2; airway responsiveness; asthma; eosinophil; prostaglandin D2