title: Synthetic double-stranded RNA enhances airway inflammation and remodelling in a rat model of asthma.
abstract: Respiratory viral infections are frequently associated with exacerbations of asthma. Double-stranded RNA (dsRNA) produced during viral infections may be one of the stimuli for exacerbation. We aimed to assess the potential effect of dsRNA on certain aspects of chronic asthma through the administration of polyinosine-polycytidylic acid (poly I:C), synthetic dsRNA, to a rat model of asthma. Brown Norway rats were sensitized to ovalbumin and challenged three times to evoke airway remodelling. The effect of poly I:C on the ovalbumin-induced airway inflammation and structural changes was assessed from bronchoalveolar lavage fluid and histological findings. The expression of cytokines and chemokines was evaluated by real-time quantitative reverse transcription PCR and ELISA. Ovalbumin-challenged animals showed an increased number of total cells and eosinophils in bronchoalveolar lavage fluid compared with PBS-challenged controls. Ovalbumin-challenged animals treated with poly I:C showed an increased number of total cells and neutrophils in bronchoalveolar lavage fluid compared with those without poly I:C treatment. Ovalbumin-challenged animals showed goblet cell hyperplasia, increased airway smooth muscle mass, and proliferation of both airway epithelial cells and airway smooth muscle cells. Treatment with poly I:C enhanced these structural changes. Among the cytokines and chemokines examined, the expression of interleukins 12 and 17 and of transforming growth factor-β(1) in ovalbumin-challenged animals treated with poly I:C was significantly increased compared with those of the other groups. Double-stranded RNA enhanced airway inflammation and remodelling in a rat model of bronchial asthma. These observations suggest that viral infections may promote airway remodelling.
authors: Department of Integrated Pulmonology, Tokyo Medical and Dental University, Tokyo, Japan. stakayama.pulm@tmd.ac.jp
authors: Satoshi
authors: S
authors: Takayama
authors: Meiyo
authors: M
authors: Tamaoka
authors: Koji
authors: K
authors: Takayama
authors: Kaori
authors: K
authors: Okayasu
authors: Kimitake
authors: K
authors: Tsuchiya
authors: Yasunari
authors: Y
authors: Miyazaki
authors: Yuki
authors: Y
authors: Sumi
authors: James G
authors: JG
authors: Martin
authors: Naohiko
authors: N
authors: Inase
mesh_terms: D056151:Airway Remodeling / Q000187:drug effects / Q000276:immunology*; D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000821:virology*; D001992:Bronchoalveolar Lavage Fluid; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000276:immunology; D004195:Disease Models, Animal; D020397:Goblet Cells / Q000187:drug effects / Q000276:immunology; D008168:Lung / Q000276:immunology; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects / Q000276:immunology; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology; D010047:Ovalbumin / Q000276:immunology; D011070:Poly I-C / Q000276:immunology / Q000494:pharmacology; D012330:RNA, Double-Stranded / Q000276:immunology* / Q000494:pharmacology; D051381:Rats
chemical_list: D016207:Cytokines; D012330:RNA, Double-Stranded; D010047:Ovalbumin; D011070:Poly I-C