Differential effects of simvastatin on IL-13-induced cytokine gene expression in primary mouse tracheal epithelial cells

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

Background: Asthma causes significant morbidity worldwide in adults and children alike, and incurs large healthcare costs. The statin drugs, which treat hyperlipidemia and cardiovascular diseases, have pleiotropic effects beyond lowering cholesterol, including immunomodulatory, anti-inflammatory, and anti-fibrotic properties which may benefit lung health. Using an allergic mouse model of asthma, we previously demonstrated a benefit of statins in reducing peribronchiolar eosinophilic inflammation, airway hyperreactivity, goblet cell hyperplasia, and lung IL-4 and IL-13 production.Objectives: In this study, we evaluated whether simvastatin inhibits IL-13-induced pro-inflammatory gene expression of asthma-related cytokines in well-differentiated primary mouse tracheal epithelial (MTE) cell cultures. We hypothesized that simvastatin reduces the expression of IL-13-inducible genes in MTE cells.Methods: We harvested tracheal epithelial cells from naïve BALB/c mice, grew them under air-liquid interface (ALI) cell culture conditions, then assessed IL-13-induced gene expression in MTE cells using a quantitative real-time PCR mouse gene array kit.Results: We found that simvastatin had differential effects on IL-13-mediated gene expression (inhibited eotaxin-1; MCP-1,-2,-3; and osteopontin (SPP1), while it induced caspase-1 and CCL20 (MIP-3α)) in MTE cells. For other asthma-relevant genes such as TNF, IL-4, IL-10, CCL12 (MCP-5), CCL5 (RANTES), and CCR3, there were no significant IL-13-inducible or statin effects on gene expression.Conclusions: Simvastatin modulates the gene expression of selected IL-13-inducible pro-inflammatory cytokines and chemokines in primary mouse tracheal epithelial cells. The airway epithelium may be a viable target tissue for the statin drugs. Further research is needed to assess the mechanisms of how statins modulate epithelial gene expression.

Original languageEnglish (US)
Article number38
JournalRespiratory Research
Volume13
DOIs
StatePublished - May 14 2012

Keywords

  • Airway epithelium
  • Asthma
  • Chemokines
  • Cytokines
  • Gene expression
  • HMG-CoA reductase
  • Mevalonate pathway
  • Mouse tracheal epithelium
  • Statin

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Fingerprint Dive into the research topics of 'Differential effects of simvastatin on IL-13-induced cytokine gene expression in primary mouse tracheal epithelial cells'. Together they form a unique fingerprint.

  • Cite this