Short-term roxithromycin treatment attenuates airway inflammation via MAPK/NF-κB activation in a mouse model of allergic asthma
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We investigated whether roxithromycin reduces ovalbumin-specific allergic asthma symptoms in mice, and we further investigated the inhibitory mechanism of roxithromycin in ovalbumin-specific allergic asthma.
Mice were divided into five groups (n = 10 for each): control group, roxithromycin-treated groups (5, 20 and 40 mg/kg) and ovalbumin-challenged group. We measured the recruitment of inflammatory cells into the bronchoalveolar lavage fluid (BALF) or the lung tissues by Kwik-Diff and hematoxylin and eosin (H&E) staining, goblet cell hyperplasia by alcian blue–periodic acid–Schiff (AB-PAS) staining, airway hyperresponsiveness (AHR) by whole-body plethysmograph chamber, cytokine and immunoglobulin E (IgE) levels by ELISA, and the activation of mitogen-activated protein (MAP) kinases and nuclear factor-kappa B (NF-κB) in the lung tissues by Western blotting.
Treatment with roxithromycin resulted in fewer inflammatory cells in the BALF and peribronchial areas, and decreased AHR, goblet cell hyperplasia, IgE levels and inflammatory cytokines, as well as MAP kinases and NF-κB activation, which are increased in lung tissues of mice with ovalbumin-induced allergic asthma.
Our data suggest that oral administration of roxithromycin suppresses ovalbumin-induced airway inflammation and AHR by regulating the inflammatory cytokines via MAP kinases/NF-κB pathway in inflammatory cells. Based on these results, we suggest that roxithromycin may be used as a therapeutic agent for allergy-induced asthma.
KeywordsAsthma Airway inflammation AHR NF-κB MAPKs
This work was supported by the National Science and Technology Supporting Plan of China (No. 2006BAD31B03-4).
- 1.Mannino DM, Homa DM, Akinbami LJ, Moorman JE, Gwynn C, Redd SC. Surveillance for asthma––United States, 1980–1999. MMWR Surveillance summaries: Morbidity and mortality weekly report. Surveillance summaries CDC. 2002; 51:1–13.Google Scholar
- 4.Robinson D, Hamid Q, Bentley A, Ying S, Kay AB, Durham SR. Activation of CD4+ T cells, increased TH2-type cytokine mRNA expression, and eosinophil recruitment in bronchoalveolar lavage after allergen inhalation challenge in patients with atopic asthma. J Allergy Clin Immunol. 1993;92:313–24.PubMedCrossRefGoogle Scholar
- 9.Hart LA, Krishnan VL, Adcock IM, Barnes PJ, Chung KF. Activation and localization of transcription factor, nuclear factor-kappaB, in asthma. Am J Resp Crit Care. 1998;158:1585–92.Google Scholar
- 35.Towbin H, Staehelin T, Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Biotechnology. 1979;24:145–9.Google Scholar