The enhanced effect of a hexameric deoxyriboguanosine run conjugation to CpG oligodeoxynucleotides on protection against allergic asthma.
BACKGROUND
Oligodeoxynucleotides containing a CpG motif (CpG ODNs), as potent inducers of T(H)1 immunity, are considered promising candidates for immune modulation in asthma. We have previously demonstrated that conjugation of a hexameric deoxyriboguanosine run to the 3' terminus (3' dG(6)-run) of phosphodiester (PE) CpG ODNs enhanced their immuno-stimulatory activities in vitro.


OBJECTIVE
This study aimed to evaluate the effect of a 3' dG(6)-run conjugation to PE or phosphorothioate (PS) CpG ODNs on protection against murine allergic asthma in vivo.


METHODS
Balb/c mice were sensitized to ovalbumin by intraperitoneal injection with or without CpG ODNs (PS CpG ODNs, PE CpG ODNs, and those with 3' dG(6)-run) and subsequently challenged with ovalbumin. We evaluated airway hyperresponsiveness, eosinophil proportion in bronchoalveolar lavage fluid, airway inflammation, and ovalbumin-specific antibody responses.


RESULTS
The conjugation of a 3' dG(6)-run to PE CpG ODNs enhanced the production of IFN-gamma from ovalbumin-specific T(H) cells and prevented the development of asthma in terms of airway hyperresponsiveness, airway eosinophilia, and ovalbumin-specific IgE responses; these effects were comparable to those of PS CpG ODNs. Enhanced effects of the 3' dG(6)-run were also observed in PS CpG ODNs, though they were lower than those in PE CpG ODNs.


CONCLUSIONS
This study suggests that conjugation of a 3' dG(6)-run to CpG ODNs might provide an effective method for immune modulation of allergic asthma.
Park
Y
Y
National Laboratory of DNA Medicine, Division of Molecular and Life Sciences, Pohang University of Science and Technology, Korea.
Chang
Y S
YS
Lee
S W
SW
Cho
S Y
SY
Kim
Y K
YK
Min
K U
KU
Kim
Y Y
YY
Cho
S H
SH
Sung
Y C
YC
D000818:Animals; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000473:pathology; D018899:CpG Islands / Q000276:immunology*; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000276:immunology*; D007111:Immunity, Cellular; D008168:Lung / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018448:Models, Immunological; D009838:Oligodeoxyribonucleotides / Q000627:therapeutic use*; D010047:Ovalbumin / Q000276:immunology; D018417:Th1 Cells
D018927:Anti-Asthmatic Agents; C408982:CPG-oligonucleotide; D009838:Oligodeoxyribonucleotides; D010047:Ovalbumin; D003849:Deoxyguanosine