CpG-oligodeoxynucleotides inhibit airway remodeling in a murine model of chronic asthma - PubMed (original) (raw)
CpG-oligodeoxynucleotides inhibit airway remodeling in a murine model of chronic asthma
Vipul V Jain et al. J Allergy Clin Immunol. 2002 Dec.
Abstract
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.
Conclusion: 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.
Similar articles
- Immunomodulatory effects of CpG oligodeoxynucleotides on house dust mite-induced airway inflammation in mice.
Hirose I, Tanaka H, Takahashi G, Wakahara K, Tamari M, Sakamoto T, Kojima S, Inagaki N, Nagai H. Hirose I, et al. Int Arch Allergy Immunol. 2008;147(1):6-16. doi: 10.1159/000128581. Epub 2008 Apr 30. Int Arch Allergy Immunol. 2008. PMID: 18446048 - Comparison of acute inflammatory and chronic structural asthma-like responses between C57BL/6 and BALB/c mice.
Van Hove CL, Maes T, Cataldo DD, Guéders MM, Palmans E, Joos GF, Tournoy KG. Van Hove CL, et al. Int Arch Allergy Immunol. 2009;149(3):195-207. doi: 10.1159/000199715. Epub 2009 Feb 12. Int Arch Allergy Immunol. 2009. PMID: 19218812 - Intranasal administration of CpG oligodeoxynucleotides reduces lower airway inflammation in a murine model of combined allergic rhinitis and asthma syndrome.
Li HT, Zhang TT, Chen ZG, Ye J, Liu H, Zou XL, Wang YH, Yang HL. Li HT, et al. Int Immunopharmacol. 2015 Sep;28(1):390-8. doi: 10.1016/j.intimp.2015.06.028. Epub 2015 Jul 9. Int Immunopharmacol. 2015. PMID: 26163938 - CpG oligodeoxynucleotides as TLR9 agonists: therapeutic application in allergy and asthma.
Gupta GK, Agrawal DK. Gupta GK, et al. BioDrugs. 2010 Aug 1;24(4):225-35. doi: 10.2165/11536140-000000000-00000. BioDrugs. 2010. PMID: 20623989 Review. - CpG DNA: immunomodulation and remodelling of the asthmatic airway.
Jain VV, Kline JN. Jain VV, et al. Expert Opin Biol Ther. 2004 Sep;4(9):1533-40. doi: 10.1517/14712598.4.9.1533. Expert Opin Biol Ther. 2004. PMID: 15335319 Review.
Cited by
- Immunotherapy of asthma using CpG oligodeoxynucleotides.
Kline JN. Kline JN. Immunol Res. 2007;39(1-3):279-86. doi: 10.1007/s12026-007-0083-2. Immunol Res. 2007. PMID: 17917072 Review. - Ma Huang Tang ameliorates bronchial asthma symptoms through the TLR9 pathway.
Jiao J, Wu J, Wang J, Guo Y, Gao L, Liang H, Huang J, Wang J. Jiao J, et al. Pharm Biol. 2018 Dec;56(1):580-593. doi: 10.1080/13880209.2018.1517184. Pharm Biol. 2018. PMID: 30415587 Free PMC article. - Intranasal CpG therapy attenuated experimental fungal asthma in a TLR9-dependent and -independent manner.
Ramaprakash H, Hogaboam CM. Ramaprakash H, et al. Int Arch Allergy Immunol. 2010;152(2):98-112. doi: 10.1159/000265531. Epub 2009 Dec 16. Int Arch Allergy Immunol. 2010. PMID: 20016192 Free PMC article. - CpG-containing immunostimulatory DNA sequences elicit TNF-alpha-dependent toxicity in rodents but not in humans.
Campbell JD, Cho Y, Foster ML, Kanzler H, Kachura MA, Lum JA, Ratcliffe MJ, Sathe A, Leishman AJ, Bahl A, McHale M, Coffman RL, Hessel EM. Campbell JD, et al. J Clin Invest. 2009 Sep;119(9):2564-76. doi: 10.1172/JCI38294. Epub 2009 Aug 10. J Clin Invest. 2009. PMID: 19726873 Free PMC article. - Loss of Bardet-Biedl syndrome proteins alters the morphology and function of motile cilia in airway epithelia.
Shah AS, Farmen SL, Moninger TO, Businga TR, Andrews MP, Bugge K, Searby CC, Nishimura D, Brogden KA, Kline JN, Sheffield VC, Welsh MJ. Shah AS, et al. Proc Natl Acad Sci U S A. 2008 Mar 4;105(9):3380-5. doi: 10.1073/pnas.0712327105. Epub 2008 Feb 25. Proc Natl Acad Sci U S A. 2008. PMID: 18299575 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical