Neural regulation of endothelial cell-mediated inflammation

Kimberly Quinlan Lindsey, S. Wright Caughman, John E. Olerud, Nigel W. Bunnett, Cheryl A. Armstrong, John C. Ansel

Research output: Contribution to journalArticle

Abstract

There is increasing evidence that the cutaneous neurosensory system can directly modulate inflammatory responses in the skin by tire release of neuropeptides such as substance P (SP). Dermal microvascular endothelial cell (DMEC) cellular adhesion molecule (CAM) expression plays a key role in directing leukocyte trafficking during cutaneous inflammatory responses. In recent studies, our laboratory examined the direct effect of SP on DMEC CAM expression and function in vitro and in vivo. Our studies indicate that DMEC express high affinity functional receptors for SP. After exposure to SP, DMEC expressed significant levels of both intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), which was accompanied by increased binding to leukocytes expressing the appropriate integrin counter receptors for these CAM. We then determined the in vivo effect of released neuropeptides on DMEC CAM expression. Our results indicate that the topical cutaneous application of the neuropeptide-releasing agent capsaicin resulted in increased ICAM-1 and VCAM-1 immunostaining of microvascular cells in the skin of human volunteers. Little is known regarding the cellular regulatory events by which SP modulates DMEC CAM expression. Our studies indicate that SP-induced cellular Ca+2 signals led to the activation of the NF-κB pathway, resulting in nuclear translocation of p65/p50 heterodimers that bind to high-affinity tandem κB sites on the VCAM-1 promoter, whereas SP activation induced NF-AT activation and ICAM-1 DNA binding. Thus, these studies further support the role of the cutaneous neurologic system in modulating inflammatory processes in the skin.

Original languageEnglish (US)
Pages (from-to)74-78
Number of pages5
JournalJournal of Investigative Dermatology Symposium Proceedings
Volume5
Issue number1
DOIs
StatePublished - 2000

Keywords

  • Cellular adhesion molecules
  • Neuropeptides
  • Substance P

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Biology
  • Dermatology
  • Cell Biology

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  • Cite this

    Lindsey, K. Q., Caughman, S. W., Olerud, J. E., Bunnett, N. W., Armstrong, C. A., & Ansel, J. C. (2000). Neural regulation of endothelial cell-mediated inflammation. Journal of Investigative Dermatology Symposium Proceedings, 5(1), 74-78. https://doi.org/10.1046/j.1087-0024.2000.00013.x