Vascular endothelial growth factor induction by rhinovirus infection.
Vascular participation manifested by a runny nose (rhinorrhea) is a prominent feature of the acute consequences of rhinovirus infection. Vascular endothelial growth factor (VEGF) is an angiogenic factor that also induces potent increases in vascular permeability; it is a candidate mediator of rhinorrhea in response to rhinovirus infection as well as contributing to enhanced vascular leakage in rhinovirus-linked asthma exacerbations. It has been shown that rhinovirus induces significant increases in both VEGF protein and mRNA in primary airway fibroblasts [Ghildyal et al. (2005): J Med Virol 75:608-615]. The current studies assessed VEGF responses to rhinovirus in primary culture airway epithelium, in epithelial and fibroblast cell lines and in rhinovirus-infected nasal secretions. Epithelial and fibroblast cells were infected with rhinovirus serotype 16 and VEGF protein and isoforms assessed by ELISA and RT-PCR, respectively. VEGF protein was released by both epithelial and fibroblast cell lines and primary airway epithelial cells in culture but was not increased following rhinovirus infection. PCR products coding for four or five of the six known VEGF isoforms were produced (121, 145, 165 and 183, and/or 189 amino acids) in cell lines and primary culture cells, but no specific isoform was linked to rhinovirus infection. Nasal VEGF was also measured in a cohort of asthmatics with verified rhinovirus and respiratory syncytial virus (RSV) infection. VEGF was not raised following rhinovirus infection alone, but was increased significantly if concomitant RSV infection was present. The data suggest that fibroblasts rather than the epithelium may play a key role in VEGF mediated vascular responses after rhinovirus infection. This may aid recruitment of inflammatory cells and contribute to airway inflammation and bronchial obstruction.
Department of Respiratory and Sleep Medicine, Monash Medical Centre, Melbourne, Australia.
Dinesha
D
De Silva
Hayat
H
Dagher
Reena
R
Ghildyal
Mandy
M
Lindsay
Xun
X
Li
Nicholas J
NJ
Freezer
John W
JW
Wilson
Philip G
PG
Bardin
D001249:Asthma / Q000150:complications / Q000378:metabolism; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000378:metabolism* / Q000821:virology; D005347:Fibroblasts / Q000378:metabolism* / Q000821:virology; D006801:Humans; D009297:Nasal Mucosa / Q000378:metabolism; D010850:Picornaviridae Infections / Q000150:complications / Q000378:metabolism* / Q000821:virology*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D012229:Rhinovirus / Q000502:physiology*; D013045:Species Specificity; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics
D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A