Respiratory syncytial virus augments production of fibroblast growth factor basic in vitro: implications for a possible mechanism of prolonged wheezing after infection.
Respiratory syncytial virus (RSV) has been linked to the development of clinical asthma. Cellular mechanisms of this observation are not yet clearly elucidated. In chronic asthma, production of growth factors and remodeling are associated with prolonged wheezing. It was hypothesized that cells infected with RSV may produce excessive levels of fibroblast growth factor basic (FGFb), and epidermal growth factor (EGF). Airway epithelial cells were incubated with either: (i) virus, (ii) inactivated virus, or (iii) media only. The levels of FGFb and EGF were measured in the cellular supernatant fluid. The study demonstrated that by 24 h after RSV inoculation, or exposure to RSV-killed virus, cells are stimulated to produce significantly more FGFb, compared with non-infected/non-exposed control cells. FGFb is an important factor in remodeling and fibroblast activation in the airway. Using treatment with actinomycin D and cylcohexamide the effect of inhibiting translation or transcription in the infected cells, on FGFb production was demonstrated. There were no alterations in EGF production detectable. Based on the findings, the mechanism of FGFb secretion after RSV inoculation, appears to be regulated at the levels of both transcription and translation. The increased FGFb release potentially could contribute to fibroblast activation and remodeling in the airway, and thus provide another possible mechanism for prolonged wheezing after infection.
Dosanjh
A
A
Pediatric Oncology Education Program, St Jude Children's Research Hospital, Memphis, TN, USA. dosamr@scripps.edu
Rednam
S
S
Martin
M
M
D001980:Bronchi / Q000166:cytology / Q000378:metabolism / Q000821:virology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D003609:Dactinomycin / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000187:drug effects / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000821:virology; D005346:Fibroblast Growth Factors / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012135:Respiratory Sounds / Q000503:physiopathology; D018357:Respiratory Syncytial Virus Infections / Q000378:metabolism / Q000503:physiopathology / Q000821:virology; D012136:Respiratory Syncytial Viruses / Q000187:drug effects / Q000502:physiology; D038301:Virus Inactivation; D014779:Virus Replication / Q000187:drug effects / Q000502:physiology
D011500:Protein Synthesis Inhibitors; D003609:Dactinomycin; D005346:Fibroblast Growth Factors; D004815:Epidermal Growth Factor