Browse > Article

Effects of CPG-oligodeoxynucleotides in Chronic Inflammation and Remodeling of Airway in a Murine Model of Bronchial Asthma  

Song, So Hyang (Department of Internal Medicine, The Catholic University of Korea)
Kim, Chi Hong (Department of Internal Medicine, The Catholic University of Korea)
Dong Hwa, Han (Research Institute of Medical Science, St. Vincent Hospital)
Kim, Seung Joon (Department of Internal Medicine, The Catholic University of Korea)
Moon, Hwa Sik (Department of Internal Medicine, The Catholic University of Korea)
Song, Jeong Sup (Department of Internal Medicine, The Catholic University of Korea)
Park, Sung Hak (Department of Internal Medicine, The Catholic University of Korea)
Publication Information
Tuberculosis and Respiratory Diseases / v.57, no.6, 2004 , pp. 543-552 More about this Journal
Abstract
Background : Airway remodeling of the asthmatic airway, the result of persistent inflammation in the bronchial wall, is associated with irreversible airway obstruction and the severity of asthma. Previous reports had represented that adminitering CpG-oligodeoxynucleotides (CpG-ODN) before sensitization or challenge by allergens inhibits the development of eosinophilic airway inflammation in a murine model of asthma, but the effects of CpG-ODNs on chronic inflammation and airway remodeling had not been characterized. To investigate the influence of CpG-ODNs on chronic inflammation and remodeling of the airway, we performed studies using a murine model of chronic allergen-induced asthma. Methods : Balb/C mice were sensitized to ovalbumin(OVA) and subsequently exposed to nebulized OVA by means of inhalation twice weekly for 7 weeks. CpG-ODNs($30{\mu}g$) was administered intraperitoneally at sensitization. After final inhalation, mice were evaluated for airway hyperresponsiveness, chronic airway inflammation and remodeling. Results : The mice exposed to chronic and recurrent airway challenge with OVA had persistent airway hyperresponsiveness, chronic inflammation and airway remodeling. Mice treated with CpG-ODNs exhibited decreased bronchial hyperresponsiveness, OVA-specific IgE, chronic inflammation and evidence of airway remodeling, including goblet cell hyperplasia and subepithelial fibrosis. Conclusion : CpG-ODNs was thought to prevent chronic inflammation and remodeling changes in a murine model of chronic asthma.
Keywords
CpG-oligodeoxynucleotides; airway remodeling; murine model of asthma;
Citations & Related Records

Times Cited By SCOPUS : 0
연도 인용수 순위
  • Reference
1 Wohlleben G, Erb KJ. Atopic disorders: a vaccine around the comer? Trends Immunol 2001;22:618-26
2 Chu RS, Tareoni OS, Kriee AM, Lehimnn PV, Harding CV. CpG oligodeoxynucleotides act as ad-juvants that switch on T helper 1 (Thl) immuoity. J Exp Med 1997;186:1623 31
3 Kline JN, Waldschmidt TJ, Businea TR, Lemiah JE, Weinstock JV, Thorne PS, et al. Modulation of airway inflammation by CpG oligodeoxynucleotides in a murine model of asthma. J Imniunol 1998:160:2555-9
4 Serebrisky D, Teper AA, Huane CK, Lee SY, ZhangTF, Schofield BH, et al. CpG oligodeoxynucel otides can reverse Th2-associated allergic airway responses and alter the B7.1/B7.2 expression in a murine model of asthma. J Immunol 2000;165:5906-12
5 Metzger WJ, Nyce JW. Olieonulceotide therapy ofallergic asthma. J Allergy Clin Immuriol 1999;104(2 pz 1):260 6
6 Tokunaga T, Yamamoto T, Yamamoto S. How BCG led to the discovery of immunostmulatory DNA. Jpn J Infect Dis 1999;52:1-11
7 Broide D, Schwarze J, Tighe H, Gifford T, Nguyen MD, Malek S, et al. Immunostimulatory DNA sequences inhibit IL-5, eosinophilic inflammation, and airway hyperresponsiveness in mice. J Immunol 1998;161(12):7054-62
8 Hartmann G, Weiner GJ, Krieg AM. CpG DNA: a potent signal for growth, activation, and maturation of human dendritic cells. Proc Natl Acad Sci USA 1999; 96:9305-10
9 Krieg AM, Yi AK, Matson S, Waldschmidt TJ, Bishop GA, Teasdale R, et al. CpG motifs in bacterial DNA trigger direct B-cell activation. Nature 1995;374:546-9
10 Wilson JW, LiX, Pain MC. The lack of distensibaity of asthmatic airways. Am Rev Respir Dis 1993;148:806-9
11 Sur S, Wad JS, Choudhury BK, Sur N, Alam R, Klinman DM. Long term prevention of allcrgic lung inflammation in a mouse model of asthma by CpG oligodeoxynucleotides. J Immunol 1999;162: 6284-93
12 Kline JN, Krieg AM, Waldschmidt TJ, Ballas ZK,Jain V, Businga TR. CpG oligodeoxynucleotides do not require THl cytokines to prevent eosinophilic airway inflammation in a murine model of asthma. J Allergy Clin Immunol 1999;104(6):1258-64
13 Kline JN, Waldschmidt TJ, Businea TR, Lemiah JE, Weinstock JV, Thorne PS, et al. Modulation of airway inflammation by CpG oligodeoxynudeotidesin a murine model of asthma. J Immunol 1998;160: 2555-9
14 Sparwasser T, Koch ES, Vabulas RM, Heee K, Lipford GB, Ellwart JW, et al. Bacterial DNA and immunostimulatory CpG oligonucleotides trigger maturation and activation of murine dendritic cells. Eur J Immunol 1998;28:2045-54
15 Rodie WR, Beaaley R, Wmlliams JH, Holeate ST. Subepithelial fibrosis in the bronchi of asthmatics. Lancet 1989;1:520 4
16 Temelkovaki J, Hoam SP, Shepherd DP, Foster PS, Kumar RK. An improved murine model of asthma: selective airway inflammation, epithelial lesions and increased methacholine responsiveness following chronic exposure to aerosolised allergen. Thorax 1998;53:849-56
17 Chu RS, Targoni OS, Krieg AM, Lehmann PV, Harding CV. CpG oligodeoxynucleotides act as adjuvants that switch on T helper 1 (Th1) immunity. J Exp Med 1997;186:1623-31
18 Tsunoda I, Tolley ND, Theil DJ, Whitton JL, Kobayashi H, Fuhinami RS. Exacerbation of viral and autoimmune animal models for multiple sclerosis by bacterial DNA. Brain Pathol 1999;9:481-93
19 Yamamoto S, Kuramoto E, Shimada S, Tokunaga T. In vitro augmentation of natural killer cell activity and production of interferon-alphq/beta and-gamma with deoxyribonucleic acid fraction from Mycobacterium bovis BCG. Jpn J Cancer Res 1988;79:866-73
20 Sun S, Zhane X, Toueh DF, Sprent J. Type I interferon-mediated stimulation of T cells by CpG DNA. J Exp Med 1998;188:2335 42
21 Warshamana GS, Martinez S, Lasky JA, Corti M, Brody AR. Dexamethasone activates expression of the PDGF-alpha receptor and induces lung fibro-blast proliferation. Am J Physiol 1998;Z74:499-507
22 Santeliz JV, Van Nest G, Traquina P, Larsen E, Waills Karp M. Amb a 1 linked CpG olieodeoxy-nueleotides reverse established airway hypeires-ponsiveness in a murine model of asthma. J Allergy Cin Immunol 2002;109(3):455-62
23 Boulet LP, Laviolette M, Turcotte H, Cartier A, Dugas M, Malo JL, et al. Bronchial subepithelial fibrosis coirelates with airway responsiveness to methadioline. Chest 1997; 112:45-52
24 Bohle B, Jahn-Schmid B, Maurer D, Kraft D, EbnerC. Oligodexoynudeotides contaming CpG motifs induce IL-12, IL-18 and INF-gamma production imcells from allergic individuals and inhibit IgEsynthesis in vitro. Eur J Immunol 1999;29:2344-53
25 Bousquet J, Cbmez P, Lacoste JY, White R, Vic P, Godard P, et al. Asthma: a disease remodeling the airways. Allerey 1992:47:3-11
26 Tanaka H, Masuda T, Tokuoka S, Komai M, Naeao K, Takahashi Y, et al. The effect of allereen-induced airway inflarmation on airway remodelling in a murine model of allergic asthma. Inflamm Res 2001;50:616 24
27 Sparwasser T, Lipford G, Miethke T, Borscherz K, Hacker H, Heegk, et al. Bacterial DNA causes septic shock. Nature 1997;386:336-7
28 Redington AE, Howarth PH. Airway wall remodeling in asthma. Thorax 1997;52:310-2
29 Jeffery PK, Goldfrey RW, Adelroth E, Nelson F, Rogers A, Johansson SA. Effects of treatment on airway inflammation and thickening of basement membrane reticular collagen in asthma. A quantita-tive light and electron microscopic study. Am Rev Respir Dis 1992; 145:890-9
30 Peng Z, Wang H, Mao X, HayGlass KT, Simons FE. CpG oligodeoxynucleotide vaccination suppresses IgE induction but may fail to down-regulate ongoing IgE responses in mice. Int Immunol 2001;13:3-11
31 Aikawa T, Shimura S, Sasaki H, Ebina M, Taki-shima T. Marked goblet cell hyperplasia with mucus accumulation in the airways of patients who died of severe acute asthma attack. Chest 1992;101: 916 21
32 Sparwaser T, Hultner L, Koch ES, Luz A, Lipford GB, Wagner H. Immunostimulatory CpG-oligode-oxynuelcleotides cause extramedullary murine hemopoiesis. J Immunol 1999;162:2368-74