Roxithromycin suppresses airway remodeling and modulates the expression of caveolin-1 and phospho-p42/p44MAPK in asthmatic rats

Int Immunopharmacol. 2015 Feb;24(2):247-255. doi: 10.1016/j.intimp.2014.11.015. Epub 2014 Nov 25.

Abstract

Roxithromycin (RXM) expresses anti-asthmatic effects that are separate from its antibiotic activity, but its effects on airway remodeling are still unknown. Here, we evaluated the effects of RXM on airway remodeling and the expression of caveolin-1 and phospho-p42/p44mitogen-activated protein kinase (phospho-p42/p44MAPK) in chronic asthmatic rats. The chronic asthma was induced by ovalbumin/Al(OH)3 sensitization and ovalbumin challenge, RXM (30mg/kg) or dexamethasone (0.5mg/kg) was given before airway challenge initiation. We measured the thickness of bronchial wall and bronchial smooth muscle cell layer to indicate airway remodeling, and caveolin-1 and phospho-p42/p44MAPK expression in lung tissue and airway smooth muscle were detected by immunohistochemistry and western blot analysis, respectively. The results demonstrated that RXM treatment decreased the thickness of bronchial wall and bronchial smooth muscle cell layer, and also downregulated the phospho-p42/p44MAPK expression and upregulated the caveolin-1 expression. The above effects of RXM were similar to dexamethasone. Our results suggested that pretreatment with RXM could suppress airway remodeling and regulate the expression of caveolin-1 and phospho-p42/p44MAPK in chronic asthmatic rats.

Keywords: Airway remodeling; Asthma; Caveolin-1; Phospho-p42/p44MAPK; Rats; Roxithromycin.

Publication types

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

MeSH terms

  • Airway Remodeling / drug effects
  • Allergens / immunology
  • Animals
  • Asthma / drug therapy*
  • Bronchi / drug effects*
  • Bronchi / pathology
  • Caveolin 1 / genetics
  • Caveolin 1 / metabolism*
  • Chronic Disease
  • Dexamethasone / pharmacology
  • Gene Expression Regulation / drug effects
  • Humans
  • Male
  • Mitogen-Activated Protein Kinase 1 / genetics
  • Mitogen-Activated Protein Kinase 1 / metabolism*
  • Mitogen-Activated Protein Kinase 3 / genetics
  • Mitogen-Activated Protein Kinase 3 / metabolism*
  • Myocytes, Smooth Muscle / drug effects*
  • Myocytes, Smooth Muscle / physiology
  • Ovalbumin / immunology
  • Rats
  • Rats, Sprague-Dawley
  • Roxithromycin / administration & dosage*
  • Roxithromycin / pharmacology

Substances

  • Allergens
  • Caveolin 1
  • Roxithromycin
  • Dexamethasone
  • Ovalbumin
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3