Macrolides attenuate mucus hypersecretion in rat airways through inactivation of NF-kappaB

Respirology. 2008 Jan;13(1):63-72. doi: 10.1111/j.1440-1843.2007.01213.x.


Background and objective: To examine the effect of a 14-membered ring macrolide on airway mucus hypersecretion in rats treated with LPS.

Methods: Mucus hypersecretion in rat airways was induced by intratracheal instillation of LPS. Rats treated with or without LPS were administered roxithromycin (1-10 mg/kg), josamycin (10 mg/kg) or amoxicillin (40 mg/kg), orally for 4 days. Expression of Muc5ac, nuclear factor (NF)-kappaB, and the mitogen-activated protein (MAP) kinases p38 and ERK1/2 in bronchial epithelium were detected by RT-PCR, immunohistochemistry or western blotting. Mucins, IL-1beta, IL-8 and tumour necrosis factor (TNF)-alpha in BAL fluid were assayed by enzyme-linked lectin assay and ELISA.

Results: LPS significantly induced the expression of Muc5ac mRNA and protein in bronchial epithelium, increased the release of mucins, IL-1beta, IL-8 and TNF-alpha, and increased neutrophil numbers in BAL. Moreover, LPS increased staining for NF-kappaB in the cytoplasm as well as nuclear translocation of NF-kappaB in airway epithelial cells. Upregulated expression of Muc5ac mRNA correlated positively with NF-kappaB activation and the levels of cytokines (P < 0.05). Roxithromycin (5 and 10 mg/kg) significantly attenuated bronchial Muc5ac expression and NF-kappaB nuclear translocation stimulated by LPS, and reduced neutrophil numbers, mucins and inflammatory cytokines in BAL (P < 0.05). However, LPS-stimulated expression of p38 and ERK1/2 in airway epithelium was not affected by roxithromycin. Josamycin and amoxicillin had no effects on Muc5ac expression, NF-kappaB activation or cytokine release.

Conclusions: Roxithromycin inhibits the pulmonary inflammatory response and airway mucus hypersecretion induced by LPS. The inhibitory effect of roxithromycin on airway mucus hypersecretion may be mediated through reduction of NF-kappaB activation, neutrophil infiltration and release of inflammatory cytokines in the lung.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amoxicillin / pharmacology
  • Animals
  • Anti-Bacterial Agents / pharmacology*
  • Josamycin / pharmacology*
  • Lipopolysaccharides
  • Male
  • Mucin 5AC
  • Mucins / genetics
  • Mucins / metabolism
  • Mucus / metabolism*
  • NF-kappa B / drug effects
  • NF-kappa B / metabolism
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Respiratory Mucosa / drug effects*
  • Respiratory Mucosa / metabolism*
  • Roxithromycin / pharmacology*


  • Anti-Bacterial Agents
  • Lipopolysaccharides
  • Muc5ac protein, rat
  • Mucin 5AC
  • Mucins
  • NF-kappa B
  • RNA, Messenger
  • Roxithromycin
  • Amoxicillin
  • Josamycin