TLR2 and TLR4 agonists induce production of the vasoactive peptide endothelin-1 by human dendritic cells

Spirig, Rolf; Potapova, Inga; Shaw-Boden, Jane; Tsui, Janice; Rieben, Robert; Shaw, Sidney G (2009). TLR2 and TLR4 agonists induce production of the vasoactive peptide endothelin-1 by human dendritic cells. Molecular immunology, 46(15), pp. 3178-82. Amsterdam: Elsevier 10.1016/j.molimm.2009.05.179

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Endothelin-1 (ET-1) is mainly secreted by endothelial cells and acts as a potent vasoconstrictor. In addition ET-1 has also been shown to have pleiotropic effects on a variety of other systems including adaptive immunity. There are two main ET-1 receptors, ET(A) and ET(B), which have different tissue and functional distributions. Dendritic cells (DC) are pivotal antigen-presenting cells linking the innate with the adaptive immune system. DC are sentinels expressing pattern-recognition receptors, e.g. the toll-like receptors (TLR) for detecting danger signals released from pathogens or tissue injury. Here we show for the first time that stimulation of human monocyte-derived DC with exogenous as well as endogenous selective TLR4 and TLR2 agonists induces the production of ET-1 in a dose- and time-dependent manner. 'Alternative' activation of DC in the presence of 1alpha,25-dihydroxyvitamin D(3) results in a marked potentiation of the endothelin response, whereas prostaglandin E(2) or dexamethasone do not increase ET-1 production. Furthermore, chetomin, an inhibitor of the transcription factor hypoxia-inducible factor 1alpha (HIF-1alpha), prevents TLR-mediated secretion of ET-1. Surprisingly, stimulation of human monocytes with LPS does not lead to secretion of detectable amounts of ET-1. These results suggest a role of ET-1 as an important player in human DC biology and innate immunity in general.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Forschungsbereich Mu50 > Forschungsgruppe Herz und Gefässe
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DCR Unit Tiefenau Hospital [discontinued] > Forschungsgruppe Vasoaktive Peptide [discontinued]

UniBE Contributor:

Spirig, Rolf; Potapova, Inga; Rieben, Robert and Shaw, Sidney

ISSN:

0161-5890

Publisher:

Elsevier

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 15:13

Last Modified:

04 May 2014 23:23

Publisher DOI:

10.1016/j.molimm.2009.05.179

PubMed ID:

19559483

Web of Science ID:

000270489800035

URI:

https://boris.unibe.ch/id/eprint/32062 (FactScience: 196920)

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