Vascular cell responsiveness to Toll-like receptor ligands in carotid atheroma

Erridge, C., Burdess, A., Jackson, A., Murray, C.A., Riggio, M.P. , Lappin, D.F., Milligan, S.G., Spickett, C.M. and Webb, D.J. (2008) Vascular cell responsiveness to Toll-like receptor ligands in carotid atheroma. European Journal of Clinical Investigation, 38(10), pp. 713-720. (doi:10.1111/j.1365-2362.2008.02010.x)

Full text not currently available from Enlighten.

Abstract

Background: Atherosclerosis is potentiated by stimulation of Toll-like receptors (TLRs), which serve to detect pathogen associated molecular patterns (PAMPs). However little is known of which PAMPs may be present in atheroma, or capable of stimulating inflammatory signalling in vascular cells.

Materials and Methods: DNA extracted from human carotid atheroma samples was amplified and sequenced using broad-range 16S gene specific primers to establish historical exposure to bacterial PAMPs. Responsiveness of primary human arterial and venous endothelial and smooth muscle cells to PAMPs specific for each of the TLRs was assessed by measurement of interleukin-8 secretion and E-selectin expression.

Results: Extracts of atheromatous tissue stimulated little or no signalling in TLR-transfected HEK-293 cells. However, sequencing of bacterial DNA amplified from carotid atheroma revealed the presence of DNA from 17 different bacterial genera, suggesting historical exposure to bacterial lipopeptide, lipopolysaccharide and flagellin. All cells examined were responsive to the ligands of TLR3 and TLR4, poly inosine:cytosine and lipopolysaccharide. Arterial cells were responsive to a wider range of PAMPs than venous cells, being additionally responsive to bacterial flagellin and unmethylated cytosine-phosphate-guanosine DNA motifs, the ligands of TLR5 and TLR9, respectively. Cells were generally unresponsive towards the ligands of human TLR7 and TLR8, loxoribine and single stranded RNA. Only coronary artery endothelial cells expressed TLR2 mRNA and responded to the TLR2 ligand Pam3CSK4.

Conclusions: Vascular cells are responsive to a relatively diverse range of TLR ligands and may be exposed, at least transiently, to ligands of TLR2, TLR4, TLR5 and TLR9 during the development of carotid atheroma.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Milligan, Mr Steve and Murray, Prof Colin and Lappin, Dr David and Riggio, Dr Marcello
Authors: Erridge, C., Burdess, A., Jackson, A., Murray, C.A., Riggio, M.P., Lappin, D.F., Milligan, S.G., Spickett, C.M., and Webb, D.J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Health and Wellbeing > Mental Health and Wellbeing
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing > Dental School
Journal Name:European Journal of Clinical Investigation
Publisher:Wiley-Blackwell Publishing Ltd.
ISSN:0014-2972
ISSN (Online):1365-2362
Published Online:20 September 2008

University Staff: Request a correction | Enlighten Editors: Update this record