Rhinovirus-induced basic fibroblast growth factor release mediates airway remodeling features

Clinical and Translational Allergy

Nikolaos G Papadopoulos¹  Sebastian L Johnston³  Dimitrios Gourgiotis¹  Dimitris Kletsas⁴  Paraskevi Maggina¹  Aurica G Telcian³  Stylianos Vittorakis²  Vassiliki Georgiou¹  Mina Gaga²  Irini S Spyridaki¹  Harris Pratsinis⁴  Eleni Volonaki¹  Stelios Psarras⁵  Chrysanthi L Skevaki¹ 

[1] UPC Research Laboratories, Allergy Department, 2nd Pediatric Clinic, University of Athens, 41 Fidipidou str, Athens, 115 27, Greece;Sotiria” Athens Chest Hospital, Athens, Greece;Imperial College London, London, UK;Institute of Biology, NCSR “Demokritos” Ag. Paraskevi, Athens, Greece;Biomedical Research Foundation, Academy of Athens, Athens, Greece

关键词: Rhinovirus;    Bronchial epithelium;    BFGF;    Asthma;    Airway remodeling;   

Others  :  794576
DOI  :  10.1186/2045-7022-2-14

 received in 2012-05-15, accepted in 2012-08-11,  发布年份 2012

【 摘 要 】

Background

Human rhinoviruses, major precipitants of asthma exacerbations, induce lower airway inflammation and mediate angiogenesis. The purpose of this study was to assess the possibility that rhinoviruses may also contribute to the fibrotic component of airway remodeling.

Methods

Levels of basic fibroblast growth factor (bFGF) mRNA and protein were measured following rhinovirus infection of bronchial epithelial cells. The profibrotic effect of epithelial products was assessed by DNA synthesis and matrix metalloproteinase activity assays. Moreover, epithelial cells were exposed to supernatants from cultured peripheral blood mononuclear cells, obtained from healthy donors or atopic asthmatic subjects and subsequently infected by rhinovirus and bFGF release was estimated. bFGF was also measured in respiratory secretions from atopic asthmatic patients before and during rhinovirus-induced asthma exacerbations.

Results

Rhinovirus epithelial infection stimulated mRNA expression and release of bFGF, the latter being positively correlated with cell death under conditions promoting rhinovirus-induced cytotoxicity. Supernatants from infected cultures induced lung fibroblast proliferation, which was inhibited by anti-bFGF antibody, and demonstrated increased matrix metalloproteinase activity. Rhinovirus-mediated bFGF release was significantly higher in an in vitro simulation of atopic asthmatic environment and, importantly, during rhinovirus-associated asthma exacerbations.

Conclusions

Rhinovirus infection induces bFGF release by airway epithelium, and stimulates stroma cell proliferation contributing to airway remodeling in asthma. Repeated rhinovirus infections may promote asthma persistence, particularly in the context of atopy; prevention of such infections may influence the natural history of asthma.

【 授权许可】

   
2012 Skevaki et al.; licensee BioMed Central Ltd.

【 图 表 】

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