TLR2 and TLR4 agonists induce production of the vasoactive peptide endothelin-1 by human dendritic cells
2009; Elsevier BV; Volume: 46; Issue: 15 Linguagem: Inglês
10.1016/j.molimm.2009.05.179
ISSN1872-9142
AutoresRolf Spirig, Inga Potapova, Jane Shaw-Boden, Janice Tsui, Robert Rieben, Sidney Shaw,
Tópico(s)Neonatal Respiratory Health Research
ResumoEndothelin-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, ETA and ETB, 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 1α,25-dihydroxyvitamin D3 results in a marked potentiation of the endothelin response, whereas prostaglandin E2 or dexamethasone do not increase ET-1 production. Furthermore, chetomin, an inhibitor of the transcription factor hypoxia-inducible factor 1α (HIF-1α), 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.
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