4-Tertiary butyl phenol exposure sensitizes human melanocytes to dendritic cell-mediated killing: relevance to vitiligo.
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.
Kroll
Tara M
TM
Department of Pathology/Oncology Institute, Loyola University, Chicago, Illinois 60153, USA.
Bommiasamy
Hemamalini
H
Boissy
Raymond E
RE
Hernandez
Claudia
C
Nickoloff
Brian J
BJ
Mestril
Ruben
R
Caroline Le Poole
I
I
D000256:Adenoviridae / Q000235:genetics; D000906:Antibodies / Q000494:pharmacology; D051017:Apoptosis Regulatory Proteins; D016923:Cell Death / Q000276:immunology; D002461:Cell Line, Transformed; D002470:Cell Survival / Q000187:drug effects; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D015870:Gene Expression; D055551:HSP27 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007509:Irritants / Q000494:pharmacology*; D008544:Melanocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism; D018832:Molecular Chaperones; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D010636:Phenols / Q000494:pharmacology*; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D012867:Skin / Q000166:cytology / Q000276:immunology; D012880:Skin Pigmentation / Q000276:immunology; D053221:TNF-Related Apoptosis-Inducing Ligand; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism; D014820:Vitiligo / Q000276:immunology / Q000473:pathology*
D000906:Antibodies; D051017:Apoptosis Regulatory Proteins; D055551:HSP27 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; D007509:Irritants; D008562:Membrane Glycoproteins; D018832:Molecular Chaperones; D009363:Neoplasm Proteins; D010636:Phenols; D018124:Receptors, Tumor Necrosis Factor; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha; C006862:butylphen