Effects of clarithromycin on cultured human nasal epithelial cells and fibroblasts.
OBJECTIVE
Long-term administration of clarithromycin has been reported to be effective in the treatment of chronic sinusitis. To investigate the mechanism underlying the anti-inflammatory activity of clarithromycin, the authors evaluated the effect of clarithromycin on the gene expression of proinflammatory cytokine and the DNA-binding activity of nuclear factor (NF)-kappa B in cultured human nasal epithelial cells and fibroblasts. Cells were incubated with endotoxin purified from nontypable Haemophilus influenzae or interleukin (IL)-1 beta in the presence of clarithromycin.


RESULTS
Northern blot analysis revealed that clarithromycin suppressed IL-1 beta gene expression in human nasal epithelial cells stimulated by H. influenzae endotoxin (HIE). Intercellular adhesion molecule-1 gene expression in nasal fibroblasts stimulated by IL-1 beta was also suppressed by clarithromycin. Furthermore, electrophoretic mobility shift assay demonstrated that clarithromycin reduced DNA-binding activity of NF-kappa B in both human nasal epithelial cells and fibroblasts stimulated by HIE or IL-1 beta, respectively.


CONCLUSIONS
The present results suggest that clarithromycin may reduce gene expression of proinflammatory cytokines and adhesion molecules from nasal mucosa at the transcriptional factor level and exert an anti-inflammatory effect on nasal mucosa in chronic sinusitis.
Miyanohara
T
T
Department of Otolaryngology, Faculty of Medicine, Kagoshima University, Japan.
Ushikai
M
M
Matsune
S
S
Ueno
K
K
Katahira
S
S
Kurono
Y
Y
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001483:Base Sequence; D015152:Blotting, Northern / Q000379:methods; D018929:Cell Culture Techniques / Q000379:methods; D002478:Cells, Cultured; D017291:Clarithromycin / Q000494:pharmacology*; D015342:DNA Probes; D004586:Electrophoresis / Q000379:methods; D004731:Endotoxins / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006193:Haemophilus influenzae; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis / Q000187:drug effects / Q000235:genetics; D007375:Interleukin-1 / Q000032:analysis / Q000235:genetics; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000032:analysis / Q000187:drug effects / Q000235:genetics; D009666:Nose / Q000166:cytology* / Q000187:drug effects*; D011994:Recombinant Proteins / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D015342:DNA Probes; D004731:Endotoxins; D007375:Interleukin-1; D016328:NF-kappa B; D011994:Recombinant Proteins; D018799:Intercellular Adhesion Molecule-1; D017291:Clarithromycin