![[The University of Leicester]](unilogo.gif)
Dr Clett Erridge
Tel: 0116 258 3048
Email: ce55@le.ac.uk
Address: Department of Cardiovascular Sciences, University of Leicester, Clinical Sciences Wing, Glenfield General Hospital, Leicester, LE3 9QP
For general enquiries, please email the secretary, Louise Goddard, or telephone 0116 258 3045.
Research interests
Atherosclerosis is a chronic inflammatory disease of the arteries that represents the root cause of the majority of heart attacks and strokes. Work in my laboratory aims to identify the primary agents responsible for promoting the inflammatory signals that underpin this disease, with a particular emphasis on investigation of the ‘PAMP hypothesis’ of atherosclerosis.
PAMPs, or ‘pathogen-associated molecular patterns’, are a family of molecules expressed by microbes but not human cells, which can be potent inducers of inflammatory signalling. The PAMP hypothesis of atherosclerosis posits that the occasional presence of PAMPs in the blood may promote the key events of atherosclerosis, namely the activation of endothelial cells, the recruitment of monocytes into the vessel wall and their transformation into lipid-laden foam cells. It is thought that we may be exposed to circulating PAMPs from 3 major potential sources: (i) common chronic infections, (ii) our commensal microbiota and (iii) the food that we eat. We are currently investigating the contribution made by each of these pathways to inflammatory processes using in vitro cell culture models and studies in human subjects.
The inflammatory responses initiated by PAMPs occur via their recognition by ‘pattern recognition receptors’ expressed on host cells, of which the Toll-like receptors (TLRs) are a major family. Our work focuses particularly on the roles played by TLRs in the regulation of processes involved in atherosclerosis, such as endothelial cell activation, monocyte recruitment, foam cell formation and lipid metabolism. We also have an active interest in the roles played by oxidised lipids in the regulation of inflammation, and the mechanisms and mediators involved in the resolution of inflammation. Our aim is to identify and develop new therapeutic approaches for the treatment or prevention of atherosclerosis and related metabolic diseases, based on an understanding of these processes. I also manage the Nutraceutical Discovery Resource.
Key Publications
Erridge C. The capacity of foodstuffs to induce innate immune activation of human monocytes in vitro is dependent on food content of stimulants of Toll-like receptors 2 and 4. Br J Nutr 2010 Jan; 20 1-9
Erridge C. Endogenous ligands of TLR2 and TLR4: agonists or assistants? J Leukoc Biol. 2010 Jun; 87 6 989-99
Erridge C, Samani NJ. Saturated fatty acids do not directly stimulate Toll-like receptor signaling. Arterioscler Thromb Vasc Biol. 2009 Nov; 29 11 1944-9
Erridge C, Burdess A, Jackson AJ, Murray C, Riggio M, Lappin D, Milligan S, Spickett CM, Webb DJ. Vascular cell responsiveness to Toll-like receptor ligands in carotid atheroma. Eur J Clin Invest. 2008 Oct 38 10 713-20
Erridge C, Kennedy S, Spickett CM, Webb DJ. Oxidized phospholipid inhibition of toll-like receptor (TLR) signaling is restricted to TLR2 and TLR4: roles for CD14, LPS-binding protein, and MD2 as targets for specificity of inhibition. J Biol Chem. 2008 Sep 5 283 36 24748-59
Erridge C. The roles of pathogen-associated molecular patterns in atherosclerosis. Trends Cardiovasc Med. 2008 Feb 18 2 52-6
Erridge C, Attina T, Spickett CM, Webb DJ. A high-fat meal induces low-grade endotoxemia: evidence of a novel mechanism of postprandial inflammation. Am J Clin Nutr. 2007 Nov 86 5 1286-92
Erridge C, Spickett CM, Webb DJ. Non-enterobacterial endotoxins stimulate human coronary artery but not venous endothelial cell activation via Toll-like receptor 2. Cardiovasc Res. 2007 Jan 1 73 1 181-9
Erridge C, Webb DJ, Spickett CM. Toll-like receptor 4 signalling is neither sufficient nor required for oxidised phospholipid mediated induction of interleukin-8 expression. Atherosclerosis. 2007 Jul 193 1 77-85
Erridge C, Stewart J, Poxton IR. Monocytes heterozygous for the Asp299Gly and Thr399Ile mutations in the Toll-like receptor 4 gene show no deficit in lipopolysaccharide signalling. J Exp Med. 2003 Jun 16 197 12 1787-91
