IgE-mediated mast cell responses are inhibited by thymol-mediated, activation-induced cell death in skin inflammation

Joshua B. Wechsler, Chia Lin Hsu, Paul J. Bryce*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

Background Mast cells play a critical role in inflammatory skin diseases through releasing proinflammatory mediators; however, few therapies directly target these cells. In 1878, the use of topical thymol, a now recognized potent agonist for transient receptor potential channels, was first described to treat eczema and psoriasis. Objective We sought to determine the mechanisms through which thymol can alter skin inflammation. Methods We examined the effect of topical thymol on IgE-dependent responses using a mast cell-dependent passive cutaneous anaphylaxis (PCA) model, as well as in vitro-cultured mast cells. Results Thymol dose-dependently inhibited PCA when administered topically 24 hours before antigen challenge but provoked an ear-swelling response directly on application. This direct effect was associated with local mast cell degranulation and was absent in histamine-deficient mice. However, unlike with PCA responses, there was no late-phase swelling. In vitro thymol directly triggered calcium flux in mast cells through transient receptor potential channel activation, along with degranulation and cytokine transcription. However, no cytokine protein was produced. Instead, thymol induced a significant increase in apoptotic cell death that was seen both in vitro and in vivo. Conclusions We propose that the efficacy of thymol in reducing IgE-dependent responses is through promotion of activation-induced apoptotic cell death of mast cells and that this likely explains the clinical benefits observed in early clinical reports.

Original languageEnglish (US)
Pages (from-to)1735-1743
Number of pages9
JournalJournal of Allergy and Clinical Immunology
Volume133
Issue number6
DOIs
StatePublished - Jun 2014

Keywords

  • Mast cell
  • calcium
  • passive cutaneous anaphylaxis
  • thymol

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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