4-Tertiary butyl phenol exposure sensitizes human melanocytes to dendritic cell-mediated killing: Relevance to vitiligo

Tara M. Kroll, Hemamalini Bommiasamy, Raymond E. Boissy, Claudia Hernandez, Brian J. Nickoloff, Ruben Mestril, I. Caroline Le Poole*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

108 Scopus citations

Abstract

The trigger initiating an autoimmune response against melanocytes in vitiligo remains unclear. Patients frequently experience stress to the skin prior to depigmentation. 4-tertiary butyl phenol (4-TBP) was used as a model compound to study the effects of stress on melanocytes. Heat shock protein (HSP)70 generated and secreted in response to 4-TBP was quantified. The protective potential of stress proteins generated following 4-TBP exposure was examined. It was studied whether HSP70 favors dendritic cell (DC) effector functions as well. Melanocytes were more sensitive to 4-TBP than fibroblasts, and HSP70 generated in response to 4-TBP exposure was partially released into the medium by immortalized vitiligo melanocyte cell line PIG3V. Stress protein HSP70 in turn induced membrane tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) expression and activation of DC effector functions towards stressed melanocytes. Melanocytes exposed to 4-TBP demonstrated elevated TRAIL death receptor expression. DC effector functions were partially inhibited by blocking antibodies to TRAIL. TRAIL expression and infiltration by CD11c+ cells was abundant in perilesional vitiligo skin. Stressed melanocytes may mediate DC activation through release of HSP70, and DC effector functions appear to play a previously unappreciated role in progressive vitiligo.

Original languageEnglish (US)
Pages (from-to)798-806
Number of pages9
JournalJournal of Investigative Dermatology
Volume124
Issue number4
DOIs
StatePublished - Apr 2005

Keywords

  • Autoimmune diseases
  • Skin pigmentation
  • TNF-related apoptosis-inducing ligand

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

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