Agonists of proteinase-activated receptor 2 induce cytokine release and activation of nuclear transcription factor κB in human dermal microvascular endothelial cells

Victoria M. Shpacovitch, Thomas Brzoska, Jörg Buddenkotte, Christoph Stroh, Christian P. Sommerhoff, John C. Ansel, Klaus Schulze-Osthoff, Nigel W. Bunnett, Thomas A. Luger, Martin Steinhoff

Research output: Contribution to journalArticle

Abstract

Proteinase-activated receptor 2 belongs to a new G protein-coupled receptor subfamily activated by various serine proteases. It has been demonstrated to play a role during inflammation of many tissues including the skin. Proteinase-activated receptor 2 is expressed by endothelial cells and regulates cutaneous inflammation in vivo. The underlying mechanisms of proteinase-activated receptor 2 activation in the skin and the effects on human dermal microvascular endothelial cells, however, are still unknown. Agonists of proteinase-activated receptor 2 such as mast cell tryptase induce widespread inflammation in many organs including the skin. Trypsinogen is generated by endothelial cells during inflammation or tumor growth. Therefore we tested whether human dermal microvascular endothelial cells express functional proteinase-activated receptor 2 and whether agonists of proteinase-activated receptor 2 regulate inflammatory responses in these cells. Calcium mobilization studies revealed that proteinase-activated receptor 2 is functional in human dermal microvascular endothelial cells. Interleukin-6 and interleukin-8 were upregulated as detected by reverse transcription polymerase chain reaction or enzyme-linked immunosorbent assay indicating a role of proteinase-activated receptor 2 in stimulating human dermal microvascular endothelial cells. Electromobility shift assays revealed proteinase-activated-receptor-2-induced activation of nuclear transcription factor κB with a maximum after 1 h. In conclusion, agonists of proteinase-activated receptor 2 upregulate interleukin-6 and interleukin-8 expression and release in human dermal microvascular endothelial cells. Thus, proteinase-activated receptor 2 may play an important role in cutaneous inflammation by mediating inflammatory responses on dermal microvascular endothelial cells and activation of nuclear transcription factor κB.

Original languageEnglish (US)
Pages (from-to)380-385
Number of pages6
JournalJournal of Investigative Dermatology
Volume118
Issue number2
DOIs
StatePublished - 2002

Keywords

  • G protein-coupled receptor
  • Inflammation
  • PAR
  • Proteases
  • Skin

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

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