Modulation of intestinal epithelial cell signalling by selenium and glutathione peroxidases. (360G-Wellcome-081380_Z_06_Z)

£214,608

Selenium is a micronutrient essential for human health. Dietary intake in the UK is suboptimal for health but the implications on disease susceptibility have not been defined. The proposed work addresses whether selenium, through the selenoprotein glutathione peroxidases, modulates inflammatory signalling pathways in colonic epithelial cells and their response to microbial challenges, and how a SNP in the glutathione peroxidase 4 gene influences these mechanisms. The effects of selenium status on inflammatory signalling pathways in Caco-2 cell lines will be assessed using targeted gene arrays, measurements of NF-KB and specific pro-inflammatory cytokines. In addition, knock-down studies using siRNA and antisense vectors will define the roles of the glutathione peroxidases 1,2,4. Since microbe-epithelium interactions are critical modulators of the inflammatory pathways, the effects of Se status and GPx1,2 and 4 knock-down on the ability of epithelial cells to respond to oxidative and microbial challenges will be investigated. A common SNP in the GPx4 gene has been linked to ulcerative colitis and leukotriene metabolism and a further goal will be to define the effects of the T and C variants of this GPx4 SNP on inflammatory pathways and responses to microbial challenges using over-expression studies in Caco-2 cells.

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Grant Details

Amount Awarded 214608
Applicant Surname Hesketh
Approval Committee Physiological Sciences Funding Committee
Award Date 2007-02-22T00:00:00+00:00
Financial Year 2006/07
Grant Programme: Title Project Grant
Internal ID 081380/Z/06/Z
Lead Applicant Prof John Hesketh
Other Applicant(s) Dr Judith Hall
Partnership Value 214608
Planned Dates: End Date 2010-09-30T00:00:00+00:00
Planned Dates: Start Date 2007-10-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region North East