TY - JOUR
T1 - Mechanism of action of 4-substituted phenols to induce vitiligo and antimelanoma immunity
AU - Kammeyer, Arthur
AU - Willemsen, Karin J.
AU - Ouwerkerk, Wouter
AU - Bakker, Walbert J.
AU - Ratsma, Danielle
AU - Pronk, Sebas D.
AU - Smit, Nico P. M.
AU - Luiten, Rosalie M.
PY - 2019
Y1 - 2019
N2 - 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.
AB - 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.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85063081248&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/30767390
U2 - https://doi.org/10.1111/pcmr.12774
DO - https://doi.org/10.1111/pcmr.12774
M3 - Article
C2 - 30767390
SN - 1755-1471
VL - 32
SP - 540
EP - 552
JO - Pigment cell & melanoma research
JF - Pigment cell & melanoma research
IS - 4
ER -