Inhibition of vascular endothelial growth factor by macrolides in cultured fibroblasts from nasal polyps.
OBJECTIVE
In order to study a new mechanism of efficacy of 14-membered ring macrolides in treating chronic rhinosinusitis, inhibitory effects of macrolides on vascular endothelial growth factor production were examined in vitro.


METHODS
Vascular endothelisal growth factor production in cultured fibloblasts from human nasal polyps obtained from surgery for chronic paranasal sinusitis stimulated by hypoxia or tumor necrosis factor-alpha was assessed under the administration of Clarithromycin or Roxisthromycin by enzyme linked immunosorbent assay and reverse transcriptase polymerase chain-reaction.


RESULTS
Dose-dependent inhibitory effects on vascular endothelisal growth factor production stimulated by hypoxia or tumor necrosis factor-alpha were noted in the groups treated with Clarithromycin and Roxisthromycin, including inhibition of vascular endothelisal growth factor mRNA levels.


CONCLUSIONS
While, to date, several evidences have indicated that the mechanisms by which 14-membered ring macrolides reduce inflammation are not simply bactericidal, these results suggest another new mechanism of efficacy of macrolides in treating chronic rhinosinusitis.
Matsune
Shoji
S
Department of Otolaryngology, Head and Neck Surgery, Field of Sensory Organology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan. shoji@m2.kufm.kagoshima-u.ac.jp
Sun
Dong
D
Ohori
Junichiro
J
Nishimoto
Kengo
K
Fukuiwa
Tatsuya
T
Ushikai
Masato
M
Kurono
Yuichi
Y
D000328:Adult; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D002478:Cells, Cultured; D017291:Clarithromycin / Q000627:therapeutic use; D005347:Fibroblasts / Q000187:drug effects* / Q000473:pathology; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D018942:Macrolides / Q000627:therapeutic use*; D009298:Nasal Polyps / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015575:Roxithromycin / Q000627:therapeutic use; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics
D000900:Anti-Bacterial Agents; D018942:Macrolides; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D015575:Roxithromycin; D017291:Clarithromycin