Mabley, JG, Pacher, P, Deb, A, Wallace, R, Elder, RH 
ORCID: https://orcid.org/0000-0003-4614-175X and Szabó, C
2005,
'Potential role for 8-oxoguanine DNA glycosylase in regulating inflammation'
, The FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 19 (2)
, pp. 290-2.
Abstract
OGG-1 DNA glycosylase (OGG-1) is an enzyme involved in DNA repair. It excises 7,8-dihydro-8-oxoguanine, which is formed by oxidative damage of guanine. We have investigated the role of OGG-1 in inflammation using three models of inflammation: endotoxic shock, diabetes, and contact hypersensitivity. We found that OGG-1(-/-) mice are resistant to endotoxin (lipopolysaccharide, LPS)-induced organ dysfunction, neutrophil infiltration and oxidative stress, when compared with the response seen in wild-type controls (OGG(+/+)). Furthermore, the deletion of the OGG-1 gene was associated with decreased serum cytokine and chemokine levels and prolonged survival after LPS treatment. Type I diabetes was induced by multiple low-dose streptozotocin treatment. OGG-1(-/-) mice were found to have significantly lower blood glucose levels and incidence of diabetes as compared with OGG-1(+/+) mice. Biochemical analysis of the pancreas showed that OGG-1(-/-) mice had greater insulin content, indicative of a greater beta-cell mass coupled with lower levels of the chemokine MIP-1alpha and Th1 cytokines IL-12 and TNF-alpha. Levels of protective Th2 cytokines, IL-4 and IL-10 were significantly higher in the pancreata of OGG-1(-/-) mice as compared with the levels measured in wild-type mice. In the contact hypersensitivity induced by oxazolone, the OGG-1(-/-) mice showed reduced neutrophil accumulation, chemokine, and Th1 and Th2 cytokine levels in the ear tissue. The current studies unveil a role for OGG-1 in the regulation of inflammation.
| Item Type: | Article |
|---|---|
| Themes: | Health and Wellbeing |
| Schools: | Schools > School of Environment and Life Sciences > Biomedical Research Centre |
| Journal or Publication Title: | The FASEB journal : official publication of the Federation of American Societies for Experimental Biology |
| Publisher: | Federation of American Society of Experimental Biology |
| Refereed: | Yes |
| ISSN: | 1530-6860 |
| Depositing User: | RH Elder |
| Date Deposited: | 06 Oct 2011 15:43 |
| Last Modified: | 27 Aug 2021 22:46 |
| URI: | https://usir.salford.ac.uk/id/eprint/17999 |
Actions (login required)
 |
Edit record (repository staff only) |
Tools
Tools