Azithromycin may inhibit interleukin-8 through suppression of Rac1 and a nuclear factor-kappa B pathway in KB cells stimulated with lipopolysaccharide.

BACKGROUND

Recent studies have shown that the 15-member macrolide antibiotic azithromycin (AZM) not only has antibacterial activity, but also results in the role of immunomodulator. Interleukin (IL)-8 is an important inflammatory mediator in periodontal disease. However, there have been no reports on the effects of AZM on IL-8 production from human oral epithelium. Therefore, we investigated the effects of AZM on IL-8 production in an oral epithelial cell line.

METHODS

KB cells were stimulated by Escherichia coli or Aggregatibacter actinomycetemcomitans (previously Actinobacillus actinomycetemcomitans) lipopolysaccharide (LPS) with or without AZM. IL-8 mRNA and protein expression and production in response to LPS were analyzed by quantitative polymerase chain reaction, flow cytometry, and enzyme-linked immunosorbent assay. The activation of nuclear factor-kappa B (NF-κB) and Rac1, which is important for IL-8 expression, was analyzed by enzyme-linked immunosorbent assay and Western blotting, respectively.

RESULTS

IL-8 mRNA expression, IL-8 production, and NF-κB activation in LPS-stimulated KB cells were inhibited by the addition of AZM. LPS-induced Rac1 activation was also suppressed by AZM.

CONCLUSIONS

This study suggests that AZM inhibits LPS-induced IL-8 production in an oral epithelial cell line, in part caused by the suppression of Rac1 and NF-κB activation. The use of AZM might provide possible benefits in periodontal therapy, with respect to both its antibacterial action and apparent anti-inflammatory effect.