This Article Full Text (PDF) Other Versions of this Article: CVI.00257-07v1 15/1/138    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Fitzner, N. Articles by Kolb-Bachofen, V. Search for Related Content PubMed PubMed Citation Articles by Fitzner, N. Articles by Kolb-Bachofen, V.

 Previous Article  |  Next Article 

Clin. Vaccine Immunol. doi:10.1128/CVI.00257-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Endothelial Cells of the Human Skin Can Express All Ten tlr-Genes and Respond to Respective Ligands

Institute of Molecular Medicine, Research Group Immunobiology, Heinrich-Heine-University, Duesseldorf, Germany; Institute of Molecular Medicine, Heinrich-Heine-University, Duesseldorf, Germany

^* To whom correspondence should be addressed. Email: bachofen{at}uni-duesseldorf.de.

	Abstract

Breakdown of the skin barrier requires recognition of and rapid responses to invading pathogens. Since wounding usually also afflicts endothelial intactness, the expression of receptors of the Toll-like family involved in pathogen recognition in human skin vessel endothelia was examined. We find that human skin-derived microvascular endothelial cells can express all 10 TLRs currently known and will respond to respective ligands.

Using immortalized skin-derived (HMEC-1) and primary dermal endothelial cells (HDMEC) we screened for TLR expression by real time PCR. Endothelial cells express eight (HMEC-1) respectively seven out of ten (HDMEC) known human TLRs under resting conditions, but can express all ten receptors in proinflammatory conditions.

To provide evidence of TLR functionality, endothelial cells were challenged with TLR ligands and – following the TLR downstream signaling – MyD88-recuitment as well as early (IL-8 release) and late immune markers (iNOS-mRNA expression) were monitored. Surprisingly, the responses observed were not uniform, but were highly specific depending of the respective TLR ligand. For instance, LPS highly increased IL-8 release, but CpG-DNA induced significant suppression. Additionally, TLR specific responses were found to differ between resting and activated endothelial cells.

These results show that human skin-derived endothelial cells can function as an important part of the innate immune response, can actively sense pathogen-associated molecular patterns and mount, increase or decrease an inflammatory signal upon exposure to any of the currently known TLR ligands. Moreover, we also show here that pro-inflammatory conditions may affect TLR expression in a specific and non-uniform pattern.