"Characterisation of Anti-Inflammatory Potential of Marine Extracts"
Research Measure: Marine Biodiscovery
Funding Type: NDP Marine Research Sub-Programme
Funding Year: 2007
Project Duration: 36 Months
Project Type: PhD Scholarship
Total Grant-Aid: €72,000
Lead Partner: Dublin City University
Project Summary:
Introduction:
Inflammatory diseases, such as inflammatory bowel disease (IBD), account for significant ill health and morbidity worldwide. The incidence of IBD in Europe is increasing and suggests that, in many parts, as many as 1 in 100 people will suffer one or more often prolonged episodes of IBD in their lifetime. IBD is a complex disease, controlled by multiple risk factors including genetic and environmental. IBD and several other inflammatory diseases are typically associated with a dysregulated type 1 T cell response (Th1) and a lack of a sufficient T regulatory response (Treg). Activated dendritic cells (DC) are responsible for the generation of these responses. Novel strategies that re-balance the excessive Th1 response and enhance Treg responses may prevent and treat such inflammatory diseases. Inflammation is also now known to be a key factor in a number of other illnesses including Alzheimer’s disease, atherosclerosis and type 2 diabetes mellitus; therefore, therapies that suppress the inflammatory responses could reduce the risk of developing a range of diseases.
Project Outline:
In the Marine Biodiscovery Proof of Concept Programme, preliminary evidence was obtained that marine extracts prepared from Bonnemesonia hamifra, Heterosiphonia japonica, Cliona clata, Alcyonium digitata and Membranipora membranacea have the ability to decrease the secretion of pro-inflammatory cytokines from murine macrophages and to increase the release of anti-inflammatory cytokines. This indicates that they possess potent anti-inflammatory potential. Given the importance of DC in generating these responses, this project will investigate the effects of fractions purified from these marine extracts, in collaboration with Prof. P. Guiry at UCD, on the activation of DC by examining their effects on cytokine production and cell surface marker expression. Furthermore, it will examine the consequences of these actions on the generation of subsequent T helper cell responses, in particular on Th1 and Treg responses. For marine extracts that yield positive results in vitro, the graduate will examine them in an in vivo murine model of inflammation (LPS shock). These studies will pinpoint the compounds in marine extracts exhibiting the greatest potential for attenuating inflammatory response and provide evidence of the mechanisms involved.