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Effects of 7,8-dihydro-8-oxo-deoxyguanosine on antigen challenge in ovalbumin-sensitized mice may be mediated by suppression of Rac
DC Field | Value | Language |
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dc.contributor.author | Ro, J. Y. | - |
dc.contributor.author | Kim, D. Y. | - |
dc.contributor.author | Lee, S-H | - |
dc.contributor.author | Park, J. W. | - |
dc.contributor.author | Chung, M-H | - |
dc.date.accessioned | 2012-07-02T06:00:12Z | - |
dc.date.available | 2012-07-02T06:00:12Z | - |
dc.date.issued | 2009-12 | - |
dc.identifier.citation | BRITISH JOURNAL OF PHARMACOLOGY; Vol.158 7; 1743-1752 | ko_KR |
dc.identifier.issn | 0007-1188 | - |
dc.identifier.uri | https://hdl.handle.net/10371/78091 | - |
dc.description.abstract | Background and purpose: Earlier we reported that 7,8-dihydro-8-oxo-deoxyguanosine (8-oxo-dG), an oxidatively modified guanine nucleoside, exerted anti-inflammatory activity through inactivation of the GTP binding protein, Rac. In the present study, the effects of 8-oxo-dG were investigated on responses to antigen challenge in sensitized mice, as Rac is also involved at several steps of the immune process including antigen-induced release of mediators from mast cells. Experimental approach: Mice were sensitized and challenged with ovalbumin without or with oral administration of 8-oxo-dG during the challenge. Effects of 8-oxo-dG were assessed by measuring lung function, cells and cytokines in broncho-alveolar lavage fluid (BALF) and serum levels of antigen-specific IgE. Rac activity in BALF cells was also measured. Key results: 8-oxo-dG inhibited the increased airway resistance and decreased lung compliance of sensitized and challenged mice to the levels of non-sensitized control mice and lowered the increased leukocytes particularly, eosinophils, in BALF. Furthermore, 8-oxo-dG suppressed allergy-associated immune responses, such as raised anti- ovalbumin IgE antibody in serum, increased expression of CD40 and CD40 ligand in lung, increased interleukin-4, -5, -13, interferon-gamma and tumour necrosis factor-alpha in BALF and mRNA levels of these cytokines in BALF cells, dose-dependently. The corresponding purine, 8-oxo-guanine, showed no effects in the same experiments. Finally, 8-oxo-dG, but not 8-oxo-guanine, inhibited the increased Rac activity in sensitized and challenged mice. Conclusion and implications: 8-Oxo-dG had anti-allergic actions that might be mediated by Rac inactivation. This compound merits further evaluation of its therapeutic potential in allergic asthma. | ko_KR |
dc.language.iso | en | ko_KR |
dc.publisher | WILEY-BLACKWELL PUBLISHING, INC | ko_KR |
dc.subject | 8-oxo-deoxyguanosine | ko_KR |
dc.subject | 8-oxo-guanine | ko_KR |
dc.subject | allergy | ko_KR |
dc.subject | cytokines | ko_KR |
dc.subject | Rac | ko_KR |
dc.subject | asthma | ko_KR |
dc.title | Effects of 7,8-dihydro-8-oxo-deoxyguanosine on antigen challenge in ovalbumin-sensitized mice may be mediated by suppression of Rac | ko_KR |
dc.type | Article | ko_KR |
dc.identifier.doi | 10.1111/j.1476-5381.2009.00436.x | - |
dc.citation.journaltitle | BRITISH JOURNAL OF PHARMACOLOGY | - |
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dc.description.tc | 7 | - |
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