Mabley, JG, Pacher, P, Deb, A, Wallace, R, Elder, RH 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.

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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:	Colleges and Schools > College of Science & Technology Colleges and Schools > College of Science & Technology > 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 16:43
Last Modified:	06 Oct 2011 16:43
URI:	http://usir.salford.ac.uk/id/eprint/17999

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