Function and survival of dendritic cells depend on endothelin-1 and endothelin receptor autocrine loops

Georgi Guruli, Beth R. Pflug, Stefana Pecher, Valeria Makarenkova, Michael R. Shurin, Joel B. Nelson

Research output: Contribution to journalArticle

45 Scopus citations


The biologic effects of endothelin-1 (ET-1) are not limited to its potent vasoconstricting activity. The endothelin receptors, ETA and ETB, have differential tissue and functional distributions. Here we showed that dendritic cells (DCs), the major antigen-presenting cells in the adaptive limb of the immune system, produce large amounts of ET-1 and significantly increase the expression of endothelin receptors upon maturation. Selective blockade of the ETA receptor significantly reduced expression of the mature DC marker CD83, decreased the production of the immunostimulatory cytokine interleukin-12, down-regulated DC ability to stimulate T cells, and promoted DC apoptosis. Selective ETB receptor blockade, on the other hand, resulted in increased expression of CD83 and improved DC survival. Therefore, ET-1/ET A/ETB autocrine/paracrine loops on DCs appear to be essential for the normal maturation and function of human DCs, presenting a unique target for immunomodulatory therapies.

Original languageEnglish (US)
Pages (from-to)2107-2115
Number of pages9
Issue number7
StatePublished - Oct 1 2004


ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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