The Role of Base Excision Repair in Regulating Endotoxin Induced Inflammation

Abstract

Endotoxins a component of the outer membrane of the cell wall of gram negative bacteria, stimulate the innate immune system to elicit an inflammatory response in mammals. Deletion of base excision repair (BER) genes has been reported to decrease the immune response to endotoxin in mouse models. It is currently unknown whether this role is limited to a few select proteins or a result of the general function of the BER pathway. The aim of this study was to identify if the loss of other BER proteins would trigger a similar response by measuring the levels of inflammatory cytokines produced and certain biomarkers of oxidative stress. To facilitate this, a new strain of NEIL1-/- mice was successfully created as well as a putative NEIL2-/- strain. A previous strain of NEIL1-/- mice displayed a sporadic obese phenotype, our NEIL1-/- mice showed no significant increase in bodyweight when compared to WT mice. Whilst there were significant differences in the serum content of cytokines IL-6, IL-12, IL-10 and IL-4 between wildtype, NEIL1-/- and OGG1-/- mice challenged with lipopolysaccharide (LPS, the active component of endotoxin). When compared to wildtype animals both NEIL1-/- and OGG1-/- mice produced lower levels of the Th1 cytokine IL-6 (♂ 1 h; p

Date of Award	1 Aug 2013
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Andrew Povey (Supervisor) & Rhoderick Elder (Supervisor)