CpG-oligodeoxynucleotides inhibit airway remodeling in a murine model of chronic asthma.
BACKGROUND
We have previously demonstrated that CpG oligodeoxynucleotides (CpG-ODNs) protect against eosinophilia and airway hyperresponsiveness in murine models of allergen-induced asthma. Acute inflammation is hypothesized to induce chronic airway responses, but no previous studies have evaluated the effects of CpG-ODNs on allergen-induced airway remodeling. Because remodeling is thought to be responsible for many of the long-term adverse effects on asthmatic patients, we evaluated whether CpG-ODNs might similarly prevent these changes using a murine model of recurrent allergen exposure.


OBJECTIVE
The purpose of this study was to evaluate the effect of CpG-ODNs on chronic inflammatory changes and airway remodeling by using a murine model of chronic allergen-induced asthma.


METHODS
C57BL/6 mice were sensitized to ovalbumin (OVA) and subsequently exposed to nebulized OVA by means of inhalation 3 times weekly for 6 weeks. Some mice received CpG-ODNs by means of intraperitoneal injection at the time of sensitization. At the end of the exposure period, mice were evaluated for the development of airway inflammation, airway hyperresponsiveness, and airway remodeling.


RESULTS
OVA-sensitized mice exposed to recurrent airway challenge with OVA have chronic inflammation, persistent airway hyperresponsiveness, and evidence of airway remodeling, including subepithelial collagen deposition and goblet cell hyperplasia-metaplasia. These changes are significantly reduced in mice treated with CpG-ODNs. Interestingly, mice treated with CpG-ODNs exhibit increased levels of bronchoalveolar lavage transforming growth factor beta, suggesting that regulatory T cells might be responsible for some of these protective effects.


CONCLUSIONS
CpG-ODNs are effective not only in preventing acute inflammation but also appear to reduce markers of airway remodeling that develop after chronic allergen exposure.
Jain
Vipul V
VV
Department of Medicine, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, USA.
Kitagaki
Kunihiko
K
Businga
Thomas
T
Hussain
Iftikhar
I
George
Caroline
C
O'shaughnessy
Patrick
P
Kline
Joel N
JN
D000818:Animals; D001249:Asthma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D001980:Bronchi / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D016535:Bronchial Hyperreactivity / Q000517:prevention & control; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002908:Chronic Disease; D003094:Collagen / Q000032:analysis; D004195:Disease Models, Animal; D004802:Eosinophilia / Q000517:prevention & control; D005260:Female; D005355:Fibrosis; D007073:Immunoglobulin E / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL; D009838:Oligodeoxyribonucleotides / Q000627:therapeutic use*; D016212:Transforming Growth Factor beta / Q000032:analysis
C408982:CPG-oligonucleotide; D009838:Oligodeoxyribonucleotides; D016212:Transforming Growth Factor beta; D007073:Immunoglobulin E; D003094:Collagen