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.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adenoviridae / genetics
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Antibodies / pharmacology
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Apoptosis Regulatory Proteins
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Cell Death / immunology
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Cell Line, Transformed
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Cell Survival / drug effects
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Dendritic Cells / cytology
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Dendritic Cells / immunology*
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Gene Expression
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HSP27 Heat-Shock Proteins
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HSP70 Heat-Shock Proteins / genetics
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HSP70 Heat-Shock Proteins / metabolism
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Heat-Shock Proteins / genetics
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Heat-Shock Proteins / metabolism
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Humans
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Irritants / pharmacology*
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Melanocytes / cytology
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Melanocytes / drug effects*
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Melanocytes / immunology
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Membrane Glycoproteins / immunology
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Membrane Glycoproteins / metabolism
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Molecular Chaperones
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Neoplasm Proteins / genetics
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Neoplasm Proteins / metabolism
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Phenols / pharmacology*
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Receptors, Tumor Necrosis Factor / metabolism
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Skin / cytology
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Skin / immunology
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Skin Pigmentation / immunology
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TNF-Related Apoptosis-Inducing Ligand
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Tumor Necrosis Factor-alpha / immunology
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Tumor Necrosis Factor-alpha / metabolism
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Vitiligo / immunology
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Vitiligo / pathology*
Substances
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Antibodies
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Apoptosis Regulatory Proteins
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HSP27 Heat-Shock Proteins
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HSP70 Heat-Shock Proteins
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HSPB1 protein, human
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Heat-Shock Proteins
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Irritants
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Membrane Glycoproteins
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Molecular Chaperones
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Neoplasm Proteins
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Phenols
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Receptors, Tumor Necrosis Factor
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TNF-Related Apoptosis-Inducing Ligand
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TNFSF10 protein, human
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Tumor Necrosis Factor-alpha
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butylphen