4-Tertiary Butyl Phenol Exposure Sensitizes Human Melanocytes to Dendritic Cell-Mediated Killing: Relevance to Vitiligo

• Published in: Journal of investigative dermatology Vol. 124; no. 4; pp. 798 - 806
• Main Authors: Kroll, Tara M., Bommiasamy, Hemamalini, Boissy, Raymond E., Hernandez, Claudia, Nickoloff, Brian J., Mestril, Ruben, Caroline Le Poole, I.
• Format: Journal Article
• Language: English
• Published: Danvers, MA Elsevier Inc 01.04.2005; Nature Publishing; Elsevier Limited
• Subjects: Adenoviridae - genetics; Antibodies - pharmacology; Apoptosis Regulatory Proteins; autoimmune diseases; Biological and medical sciences; Cell Death - immunology; Cell Line, Transformed; Cell Survival - drug effects; Dendritic Cells - cytology; Dendritic Cells - immunology; Dermatology; Gene Expression; Heat-Shock Proteins - genetics; Heat-Shock Proteins - metabolism; HSP27 Heat-Shock Proteins; HSP70 Heat-Shock Proteins - genetics; HSP70 Heat-Shock Proteins - metabolism; Humans; Irritants - pharmacology; Medical sciences; Melanocytes - cytology; Melanocytes - drug effects; Melanocytes - immunology; Membrane Glycoproteins - immunology; Membrane Glycoproteins - metabolism; Neoplasm Proteins - genetics; Neoplasm Proteins - metabolism; Phenols - pharmacology; Pigmentary diseases of the skin; Receptors, Tumor Necrosis Factor - metabolism; Skin - cytology; Skin - immunology; skin pigmentation; Skin Pigmentation - immunology; TNF-Related Apoptosis-Inducing Ligand; Tumor Necrosis Factor-alpha - immunology; Tumor Necrosis Factor-alpha - metabolism; Vitiligo - immunology; Vitiligo - pathology; autoimmune diseases; TNF-related apoptosis-inducing ligand; skin pigmentation; Human; Dendritic cell; Skin disease; Pigmentation disorder; Dermatology; Melanocyte; Autoimmune disease; Exposure; Pigmentation; Phenol; Vitiligo; Antigen presenting cell; Phenols; TNF related apoptosis inducing ligand; Sensitization; autoimmune diseases/skin pigmentation/TNF-related apoptosis-inducing ligand
• ISSN: 0022-202X; 1523-1747
• DOI: 10.1111/j.0022-202X.2005.23653.x

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.