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Induction of TLR2 expression by inflammatory stimuli is required for endothelial cell responses to lipopeptides.
Mol Immunol. 2008 Nov; 46(1):145-57.MI

Abstract

Human endothelial cells (EC) express Toll-like receptor 4 (TLR4), a receptor for lipopolysaccharides (LPS), but little or no TLR2, a lipopeptide receptor. The aim of this study was to investigate to what extent inflammatory stimuli modify the expression by EC of TLR4 and TLR2, of the TLR2 co-receptors TLR1 and TLR6 and of the TLR2-accessory proteins CD14 and CD36. Stimulation of umbilical vein derived EC with TNF-alpha, LPS or IL-1beta for 24h induced a strong increase in TLR2 mRNA but not in TLR1, TLR4 and TLR6 mRNA. Inflammatory activation had little effect on CD14 mRNA, but decreased the expression of CD36 mRNA. TLR2 antigen was readily detected by flow cytometry on activated EC, but not on resting EC. A significant proportion of TLR2 was found to be located intracellularly. By using specific signalling pathway inhibitors we established that the induction of TLR2 by inflammatory stimuli was dependent on NF-kappaB, p38-MAP kinase and c-Jun kinase. IRAK-1 phosphorylation after treatment with 10mug/ml of lipoteichoic acid (LTA), a TLR2 agonist, was only observed in TNF-alpha-stimulated EC and not in resting EC. Furthermore, LTA potentiated the increase of the inflammatory markers E-Selectin or IL-8 in EC pre-treated with TNF-alpha, LPS or IL-1beta, but not in resting EC. These results imply that the up-regulated TLR2 is functionally active. Interestingly, LTA had no effect on TLR2 expression, nor maintained TLR2 expression, in activated EC. This suggests that lipopeptide responses of EC are dependent on the continued presence of inflammatory cytokines, provided by other cell types, or LPS. In conclusion, inflammatory stimuli induce a high TLR2 expression in EC, which in turn enables the cells to strongly respond to lipopeptides. The up-regulation of TLR2 may be of relevance for the vascular effects of Gram-positive bacteria.

Authors+Show Affiliations

Division of Angiology and Hemostasis, University Hospital of Geneva, Faculty of Medicine, 24, Rue Micheli-du-Crest, 1211 Geneva 14, Switzerland.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18722665

Citation

Satta, Nathalie, et al. "Induction of TLR2 Expression By Inflammatory Stimuli Is Required for Endothelial Cell Responses to Lipopeptides." Molecular Immunology, vol. 46, no. 1, 2008, pp. 145-57.
Satta N, Kruithof EK, Reber G, et al. Induction of TLR2 expression by inflammatory stimuli is required for endothelial cell responses to lipopeptides. Mol Immunol. 2008;46(1):145-57.
Satta, N., Kruithof, E. K., Reber, G., & de Moerloose, P. (2008). Induction of TLR2 expression by inflammatory stimuli is required for endothelial cell responses to lipopeptides. Molecular Immunology, 46(1), 145-57. https://doi.org/10.1016/j.molimm.2008.07.017
Satta N, et al. Induction of TLR2 Expression By Inflammatory Stimuli Is Required for Endothelial Cell Responses to Lipopeptides. Mol Immunol. 2008;46(1):145-57. PubMed PMID: 18722665.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Induction of TLR2 expression by inflammatory stimuli is required for endothelial cell responses to lipopeptides. AU - Satta,Nathalie, AU - Kruithof,Egbert K O, AU - Reber,Guido, AU - de Moerloose,Philippe, Y1 - 2008/08/23/ PY - 2008/05/21/received PY - 2008/07/15/revised PY - 2008/07/15/accepted PY - 2008/8/30/pubmed PY - 2009/4/9/medline PY - 2008/8/30/entrez SP - 145 EP - 57 JF - Molecular immunology JO - Mol Immunol VL - 46 IS - 1 N2 - Human endothelial cells (EC) express Toll-like receptor 4 (TLR4), a receptor for lipopolysaccharides (LPS), but little or no TLR2, a lipopeptide receptor. The aim of this study was to investigate to what extent inflammatory stimuli modify the expression by EC of TLR4 and TLR2, of the TLR2 co-receptors TLR1 and TLR6 and of the TLR2-accessory proteins CD14 and CD36. Stimulation of umbilical vein derived EC with TNF-alpha, LPS or IL-1beta for 24h induced a strong increase in TLR2 mRNA but not in TLR1, TLR4 and TLR6 mRNA. Inflammatory activation had little effect on CD14 mRNA, but decreased the expression of CD36 mRNA. TLR2 antigen was readily detected by flow cytometry on activated EC, but not on resting EC. A significant proportion of TLR2 was found to be located intracellularly. By using specific signalling pathway inhibitors we established that the induction of TLR2 by inflammatory stimuli was dependent on NF-kappaB, p38-MAP kinase and c-Jun kinase. IRAK-1 phosphorylation after treatment with 10mug/ml of lipoteichoic acid (LTA), a TLR2 agonist, was only observed in TNF-alpha-stimulated EC and not in resting EC. Furthermore, LTA potentiated the increase of the inflammatory markers E-Selectin or IL-8 in EC pre-treated with TNF-alpha, LPS or IL-1beta, but not in resting EC. These results imply that the up-regulated TLR2 is functionally active. Interestingly, LTA had no effect on TLR2 expression, nor maintained TLR2 expression, in activated EC. This suggests that lipopeptide responses of EC are dependent on the continued presence of inflammatory cytokines, provided by other cell types, or LPS. In conclusion, inflammatory stimuli induce a high TLR2 expression in EC, which in turn enables the cells to strongly respond to lipopeptides. The up-regulation of TLR2 may be of relevance for the vascular effects of Gram-positive bacteria. SN - 0161-5890 UR - https://www.unboundmedicine.com/medline/citation/18722665/Induction_of_TLR2_expression_by_inflammatory_stimuli_is_required_for_endothelial_cell_responses_to_lipopeptides_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0161-5890(08)00298-8 DB - PRIME DP - Unbound Medicine ER -