The effects of endothelin-1 on degranulation, cytokine, and growth factor production by skin-derived mast cells

Eur J Immunol. 2004 Jul;34(7):1910-9. doi: 10.1002/eji.200424912.


Endothelin-1 (ET-1), originally described as a vasoconstrictor, is now known to be involved in pathogenesis of various disorders including vascular, inflammatory, and fibrotic diseases. Recent studies suggest that mast cells are also involved in the same pathological conditions. In this study, we tested a hypothesis that ET-1 would affect mast cell functions and contribute to such disease conditions, using fetal skin-derived cultured mast cells (FSMC) and bone marrow-derived cultured mast cells (BMMC). FSMC expressed ET receptors (ET(A) and ET(B)) at mRNA and protein levels, whereas BMMC expressed lower levels of ET(A), and little, if any, ET(B). ET-1 induced degranulation by FSMC, but not by BMMC through ET(A)-mediated pathways. ET-1 at different concentrations exerted the reciprocal effects on degranulation by IgE-bound FSMC. Furthermore, ET-1 induced TNF-alpha and IL-6 production by FSMC, but not by BMMC, and significantly enhanced VEGF production and TGF-beta1 mRNA expression by FSMC. Finally, ET-1 was produced by FSMC, but not by BMMC in response to Toll-like receptor ligands. These results indicate contrasting impacts of ET-1 on distinct mast cell populations. We propose that ET-1 may participate in pathological conditions of various disorders via its multi-functional effects on mast cells under certain conditions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Degranulation / drug effects*
  • Cells, Cultured
  • Cytokines / biosynthesis*
  • Endothelin-1 / biosynthesis
  • Endothelin-1 / pharmacology*
  • Growth Substances / biosynthesis*
  • Immunoglobulin E / immunology
  • Immunoglobulin E / metabolism
  • Ligands
  • Mast Cells / drug effects*
  • Mast Cells / metabolism*
  • Membrane Glycoproteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, Cell Surface / metabolism
  • Receptors, Endothelin / genetics
  • Receptors, Endothelin / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Skin* / cytology
  • Toll-Like Receptors


  • Cytokines
  • Endothelin-1
  • Growth Substances
  • Ligands
  • Membrane Glycoproteins
  • RNA, Messenger
  • Receptors, Cell Surface
  • Receptors, Endothelin
  • Toll-Like Receptors
  • Immunoglobulin E