The Effect of CpG-Oligodeoxynucleotides with Different Backbone Structures and 3' Hexameric Deoxyriboguanosine Run Conjugation on the Treatment of Asthma in Mice.
10.3346/jkms.2009.24.5.860
- Author:
Yoon Seok CHANG
1
;
Yoon Keun KIM
;
Hyouk Soo KWON
;
Heung Woo PARK
;
Kyung Up MIN
;
You Young KIM
;
Sang Heon CHO
Author Information
1. Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
Asthma;
Models, Animal;
Allergy;
Immunotherapy;
CpG-ODN;
Poly G
- MeSH:
Animals;
Anti-Asthmatic Agents/*therapeutic use;
Asthma/*drug therapy/physiopathology;
Bronchial Hyperreactivity/drug therapy;
Bronchoalveolar Lavage Fluid/immunology;
Deoxyguanosine/*analogs & derivatives/*chemistry;
Female;
Immunoglobulin G/metabolism;
Interleukin-12/analysis;
Interleukin-4/analysis;
Interleukin-5/analysis;
Lung/pathology;
Mice;
Mice, Inbred BALB C;
Oligodeoxyribonucleotides/*therapeutic use;
Phosphorothioate Oligonucleotides/therapeutic use;
Splenomegaly/pathology
- From:Journal of Korean Medical Science
2009;24(5):860-866
- CountryRepublic of Korea
- Language:English
-
Abstract:
CpG-Oligodeoxynucleotide (ODN) has two backbones. Phosphorothioate backbone (PS) shows a strong immunostimulating effect while phosphodiester (PE) shows little in vivo. 3' hexameric deoxyriboguanosine-run (3' dG6-run) conjugation to PE CpG-ODN has been reported to enhance immunostimulation and to protect against asthma when injected at the time of sensitization in mice. We evaluated the treatment effects of PE and PS CpG-ODN with or without 3' dG6-run on asthma in presensitized mice. BALB/c mice sensitized with ovalbumin and alum were challenged with 1% ovalbumin on three days. CpG-ODNs (100 microgram) or PBS were injected 4 times; 27 hr before challenge and 3 hr before each challenge (CpG-dG6: CpG-ODN with 3' dG6-run, PE*-CpG-dG6: PE-CpG-dG6 with two PS backbones at the 5' terminus). PE-CpG showed no treatment effect. PE-CpG-dG6 only increased ovalbumin-specific IgG2a. PE*-CpG-dG6 increased ovalbumin-specific IgG2a but also reduced BAL fluid eosinophils and airway hyperresponsiveness. PS-CpG increased ovalbumin-specific IgG2a, reduced airway inflammation and airway hyperresponsiveness. PS-CpG-dG6 was less effective than PS-CpG on airway inflammation and airway hyperresponsiveness. In pre-sensitized mice, PE-CpG required not only 3' dG6-run but also the modification of two PS linkages at 5' terminus to inhibit features of asthma. PS-CpG was strong enough to inhibit asthma but PS-CpG-dG6 was less effective.
