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The Effect of CpG-Oligodeoxynucleotides with Different Backbone Structures and 3' Hexameric Deoxyriboguanosine Run Conjugation on the Treatment of Asthma in Mice

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' dG(6)-run) conjugation to PE CpG-ODN has been reported to enhance immunostimulati...

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Autores principales: Chang, Yoon-Seok, Kim, Yoon-Keun, Kwon, Hyouk-Soo, Park, Heung-Woo, Min, Kyung-Up, Kim, You-Young, Cho, Sang-Heon
Formato: Texto
Lenguaje:English
Publicado: The Korean Academy of Medical Sciences 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2752769/
https://www.ncbi.nlm.nih.gov/pubmed/19794984
http://dx.doi.org/10.3346/jkms.2009.24.5.860
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author Chang, Yoon-Seok
Kim, Yoon-Keun
Kwon, Hyouk-Soo
Park, Heung-Woo
Min, Kyung-Up
Kim, You-Young
Cho, Sang-Heon
author_facet Chang, Yoon-Seok
Kim, Yoon-Keun
Kwon, Hyouk-Soo
Park, Heung-Woo
Min, Kyung-Up
Kim, You-Young
Cho, Sang-Heon
author_sort Chang, Yoon-Seok
collection PubMed
description 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' dG(6)-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' dG(6)-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 µg) or PBS were injected 4 times; 27 hr before challenge and 3 hr before each challenge (CpG-dG(6): CpG-ODN with 3' dG(6)-run, PE*-CpG-dG(6): PE-CpG-dG(6) with two PS backbones at the 5' terminus). PE-CpG showed no treatment effect. PE-CpG-dG(6) only increased ovalbumin-specific IgG2a. PE*-CpG-dG(6) 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-dG(6) was less effective than PS-CpG on airway inflammation and airway hyperresponsiveness. In pre-sensitized mice, PE-CpG required not only 3' dG(6)-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-dG(6) was less effective.
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spelling pubmed-27527692009-10-01 The Effect of CpG-Oligodeoxynucleotides with Different Backbone Structures and 3' Hexameric Deoxyriboguanosine Run Conjugation on the Treatment of Asthma in Mice Chang, Yoon-Seok Kim, Yoon-Keun Kwon, Hyouk-Soo Park, Heung-Woo Min, Kyung-Up Kim, You-Young Cho, Sang-Heon J Korean Med Sci Original Article 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' dG(6)-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' dG(6)-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 µg) or PBS were injected 4 times; 27 hr before challenge and 3 hr before each challenge (CpG-dG(6): CpG-ODN with 3' dG(6)-run, PE*-CpG-dG(6): PE-CpG-dG(6) with two PS backbones at the 5' terminus). PE-CpG showed no treatment effect. PE-CpG-dG(6) only increased ovalbumin-specific IgG2a. PE*-CpG-dG(6) 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-dG(6) was less effective than PS-CpG on airway inflammation and airway hyperresponsiveness. In pre-sensitized mice, PE-CpG required not only 3' dG(6)-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-dG(6) was less effective. The Korean Academy of Medical Sciences 2009-10 2009-09-23 /pmc/articles/PMC2752769/ /pubmed/19794984 http://dx.doi.org/10.3346/jkms.2009.24.5.860 Text en Copyright © 2009 The Korean Academy of Medical Sciences http://creativecommons.org/licenses/by-nc/3.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Chang, Yoon-Seok
Kim, Yoon-Keun
Kwon, Hyouk-Soo
Park, Heung-Woo
Min, Kyung-Up
Kim, You-Young
Cho, Sang-Heon
The Effect of CpG-Oligodeoxynucleotides with Different Backbone Structures and 3' Hexameric Deoxyriboguanosine Run Conjugation on the Treatment of Asthma in Mice
title The Effect of CpG-Oligodeoxynucleotides with Different Backbone Structures and 3' Hexameric Deoxyriboguanosine Run Conjugation on the Treatment of Asthma in Mice
title_full The Effect of CpG-Oligodeoxynucleotides with Different Backbone Structures and 3' Hexameric Deoxyriboguanosine Run Conjugation on the Treatment of Asthma in Mice
title_fullStr The Effect of CpG-Oligodeoxynucleotides with Different Backbone Structures and 3' Hexameric Deoxyriboguanosine Run Conjugation on the Treatment of Asthma in Mice
title_full_unstemmed The Effect of CpG-Oligodeoxynucleotides with Different Backbone Structures and 3' Hexameric Deoxyriboguanosine Run Conjugation on the Treatment of Asthma in Mice
title_short The Effect of CpG-Oligodeoxynucleotides with Different Backbone Structures and 3' Hexameric Deoxyriboguanosine Run Conjugation on the Treatment of Asthma in Mice
title_sort effect of cpg-oligodeoxynucleotides with different backbone structures and 3' hexameric deoxyriboguanosine run conjugation on the treatment of asthma in mice
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2752769/
https://www.ncbi.nlm.nih.gov/pubmed/19794984
http://dx.doi.org/10.3346/jkms.2009.24.5.860
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