Rhinovirus-induced basic fibroblast growth factor release mediates airway remodeling features.
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.
UPC Research Laboratories, Allergy Department, 2nd Pediatric Clinic, University of Athens, 41 Fidipidou str, Athens, 115 27, Greece. cskevaki@allergy.gr.
Chrysanthi L
CL
Skevaki
Stelios
S
Psarras
Eleni
E
Volonaki
Harris
H
Pratsinis
Irini S
IS
Spyridaki
Mina
M
Gaga
Vassiliki
V
Georgiou
Stylianos
S
Vittorakis
Aurica G
AG
Telcian
Paraskevi
P
Maggina
Dimitris
D
Kletsas
Dimitrios
D
Gourgiotis
Sebastian L
SL
Johnston
Nikolaos G
NG
Papadopoulos