Budesonide suppresses pulmonary antibacterial host defense by down-regulating cathelicidin-related antimicrobial peptide in allergic inflammation mice and in lung epithelial cells.

Abstract

BACKGROUND:

Glucocorticoids are widely regarded as the most effective treatment for asthma. However, the direct impact of glucocorticoids on the innate immune system and antibacterial host defense during asthma remain unclear. Understanding the mechanisms underlying this process is critical to the clinical application of glucocorticoids for asthma therapy. After sensitization and challenge with ovalbumin (OVA), BALB/c mice were treated with inhaled budesonide and infected with Pseudomonas aeruginosa (P. aeruginosa). The number of viable bacteria in enflamed lungs was evaluated, and levels of interleukin-4 (IL-4) and interferon-γ (IFN-γ) in serum were measured. A lung epithelial cell line was pretreated with budesonide. Levels of cathelicidin-related antimicrobial peptide (CRAMP) were measured by immunohistochemistry and western blot analysis. Intracellular bacteria were observed in lung epithelial cells.

RESULTS:

Inhaled budesonide enhanced lung infection in allergic mice exposed to P. aeruginosa and increased the number of viable bacteria in lung tissue. Higher levels of IL-4 and lower levels of IFN-γ were observed in the serum. Budesonide decreased the expression of CRAMP, increased the number of internalized P. aeruginosa in OVA-challenged mice and in lung epithelial cell lines. These data indicate that inhaled budesonide can suppress pulmonary antibacterial host defense by down-regulating CRAMP in allergic inflammation mice and in cells in vitro.

CONCLUSIONS:

Inhaled budesonide suppressed pulmonary antibacterial host defense in an asthmatic mouse model and in lung epithelium cells in vitro. This effect was dependent on the down-regulation of CRAMP.

• Authors: Peng Wang, Xiaoyun Wang, Xiaoqiong Yang, Zhigang Liu, Min Wu, Guoping Li
• Journal: BMC immunology (BMC Immunol) Vol. 14 Pg. 7 (Feb 06 2013) ISSN: 1471-2172 [Electronic] England
• PMID: 23387852 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Bacterial Agents
• Antimicrobial Cationic Peptides
• Cathelicidins
• Interleukin-4
• Budesonide
• Interferon-gamma
• Ovalbumin

Topics

• Animals
• Anti-Bacterial Agents (pharmacology)
• Antimicrobial Cationic Peptides
• Budesonide (pharmacology, therapeutic use)
• Cathelicidins (metabolism)
• Colony Count, Microbial
• Down-Regulation (drug effects)
• Epithelial Cells (drug effects, immunology, microbiology, pathology)
• Host-Pathogen Interactions (drug effects, immunology)
• Hypersensitivity (complications, immunology, pathology)
• Immunosuppression Therapy
• Inflammation (drug therapy, immunology, microbiology, pathology)
• Interferon-gamma (blood)
• Interleukin-4 (blood, metabolism)
• Lung (drug effects, immunology, microbiology, pathology)
• Mice
• Mice, Inbred BALB C
• Ovalbumin (immunology)
• Pseudomonas Infections (drug therapy, immunology, microbiology, pathology)
• Pseudomonas aeruginosa (drug effects, growth & development)