Mechanism of action of 4-substituted phenols to induce vitiligo and antimelanoma immunity.

Abstract:

:Monobenzone is a 4-substituted phenol that can induce vitiligo and antimelanoma immunity. We investigated the influence of the chemical structure on the biological activity of a series of structurally related 4-substituted phenols. All phenols inhibited cellular melanin synthesis, and eight of ten phenols inhibited tyrosinase activity, using the MBTH assay. These phenols also induced glutathione (GSH) depletion, indicative of quinone formation and protein thiol binding, which can increase the immunogenicity of melanosomal proteins. Specific T-cell activation was found upon stimulation with phenol-exposed pigmented cells, which also reacted with unexposed cells. In contrast, 4-tertbutylphenol induced immune activation was not restricted to pigment cells, analogous to contact sensitization. We conclude that 4-substituted phenols can induce specific T-cell responses against melanocytes and melanoma cells, also acting at distant, unexposed body sites, and may confer a risk of chemical vitiligo. Conversely, these phenols may be applicable to induce specific antimelanoma immunity.

authors

Kammeyer A,Willemsen KJ,Ouwerkerk W,Bakker WJ,Ratsma D,Pronk SD,Smit NPM,Luiten RM

doi

10.1111/pcmr.12774

subject

Has Abstract

pub_date

2019-07-01 00:00:00

pages

540-552

issue

4

eissn

1755-1471

issn

1755-148X

journal_volume

32

pub_type

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