Τίτλος:
Rhinovirus-induced basic fibroblast growth factor release mediates airway remodeling features
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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. © 2012 Skevaki et al.; licensee BioMed Central Ltd.
Συγγραφείς:
Skevaki, C.L.
Psarras, S.
Volonaki, E.
Pratsinis, H.
Spyridaki, I.S.
Gaga, M.
Georgiou, V.
Vittorakis, S.
Telcian, A.G.
Maggina, P.
Kletsas, D.
Gourgiotis, D.
Johnston, S.L.
Papadopoulos, N.G.
Περιοδικό:
Clinical and Translational Allergy
Εκδότης:
BioMed Central Ltd.
Λέξεις-κλειδιά:
fibroblast growth factor 2; matrix metalloproteinase, airway remodeling; allergic asthma; Article; assay; bFGF gene; bronchial epithelial cell; cell death; cell proliferation; controlled study; correlational study; cytotoxicity; disease exacerbation; DNA synthesis assay; enzyme activity; epithelium cell; fibrosis; gene expression; human; human cell; in vitro study; lung fibroblast; matrix metalloproteinase activity assay; nonhuman; priority journal; protein secretion; Rhinovirus; Rhinovirus infection; simulation; upregulation
DOI:
10.1186/2045-7022-2-14
