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Mechanism of action of 4‐substituted phenols to induce vitiligo and antimelanoma immunity
Author(s) -
Kammeyer Arthur,
Willemsen Karin J.,
Ouwerkerk Wouter,
Bakker Walbert J.,
Ratsma Danielle,
Pronk Sebas D.,
Smit Nico P. M.,
Luiten Rosalie M.
Publication year - 2019
Publication title -
pigment cell and melanoma research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.618
H-Index - 105
eISSN - 1755-148X
pISSN - 1755-1471
DOI - 10.1111/pcmr.12774
Subject(s) - vitiligo , phenols , chemistry , tyrosinase , sensitization , cellular immunity , melanin , immunity , glutathione , phenol , cytotoxicity , biochemistry , immune system , biology , immunology , in vitro , enzyme , organic chemistry
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.