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

BMC Immunology

Guoping Li⁴  Min Wu³  Zhigang Liu⁴  Xiaoqiong Yang⁵  Xiaoyun Wang²  Peng Wang¹ 

[1] Bao Ji Central Hospital, Bao Ji, Shan Xi, 721008, China;Inflammations & Allergic Diseases Research Unit, Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan, 646000, China;Department of Biochemistry and Molecular Biology, University of North Dakota, 501 N Columbia Rd, EJRF Building Room 2726, Grand Forks, North Dakota, 58203-9037, USA;State Key Laboratory of Respiratory Disease for Allergy at Shenzhen University, School of Medicine, Shenzhen University, Nanhai Ave 3688, Shenzhen, Guangdong, 518060, PR China;Department of Respiratory Disease, Affiliated Hospital of Luzhou Medical College, Luzhou, 646000, China

关键词: Budesonide;    Cathelicidin;    Antibacterial host defense;    Allergic airway inflammation;   

Others  :  1077840
DOI  :  10.1186/1471-2172-14-7

 received in 2012-07-17, accepted in 2013-02-04,  发布年份 2013

【 摘 要 】

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.

【 授权许可】

   
2013 Wang et al; licensee BioMed Central Ltd.

【 图 表 】

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