Synergistic effects of fluticasone propionate and salmeterol on inhibiting rhinovirus-induced epithelial production of remodelling-associated growth factors.
BACKGROUND
Rhinoviruses (RV), the major trigger of acute asthma exacerbations, are able to infect bronchial epithelium and induce production of pro-inflammatory, but also angiogenic and pro-fibrotic mediators. Fluticasone propionate (FP) and salmeterol (S) are clinically effective and act synergistically in controlling persistent asthma; however, their effect on virus-associated asthma is less clear.


OBJECTIVE
The aim of this study was to assess the individual and combined effects of FP and S on RV-induced epithelial production of vascular endothelial growth factor (VEGF) and fibroblast growth factor-2 (FGF-2).


METHODS
Bronchial epithelial cells (BEAS-2B) were exposed in vitro to RV and were subsequently treated with FP and S, at physiologically relevant concentrations, alone or in combination. VEGF and FGF-2 were measured in the supernatants of these cultures using ELISA.


RESULTS
FP was able to reduce RV-induced VEGF production in a dose-dependent manner. S also induced a smaller reduction; addition of both factors inhibited VEGF synergistically. FGF-2 production was not inhibited by either FP or S alone, but was significantly reduced when both substances were present in the culture.


CONCLUSIONS
This study demonstrates that FP and S may synergistically inhibit the production of angiogenic and/or pro-fibrotic factors that are induced after RV infection of BEAS-2B and are implicated in airway remodelling, suggesting that this combination may represent an important therapeutic option on virus-induced asthma.
Volonaki
E
E
Allergy Department, 2nd Pediatric Clinic, University of Athens, Athens, Greece.
Psarras
S
S
Xepapadaki
P
P
Psomali
D
D
Gourgiotis
D
D
Papadopoulos
N G
NG
D000420:Albuterol / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000730:Androstadienes / Q000627:therapeutic use*; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001980:Bronchi / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D016222:Fibroblast Growth Factor 2 / Q000032:analysis / Q000378:metabolism; D000068298:Fluticasone; D006367:HeLa Cells; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000032:analysis / Q000378:metabolism*; D010850:Picornaviridae Infections / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D012229:Rhinovirus; D000068299:Salmeterol Xinafoate; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis / Q000378:metabolism
D000730:Androstadienes; D000893:Anti-Inflammatory Agents; D036341:Intercellular Signaling Peptides and Proteins; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D000068299:Salmeterol Xinafoate; D000068298:Fluticasone; D000420:Albuterol