S100B as a potential biomarker for the detection of cytotoxicity of melanocytes.
Skin irritation is one of the most common adverse reactions in hydroquinone (HQ) and retinoic acid (RA). Although melanocytes have rarely been considered to be involved in skin irritation, RA and particularly HQ could induce melanocyte toxicity, resulting in depigmentation. We chose S100B as a candidate gene for melanocytotoxicity from a genome-wide transcriptional profiling analysis after applying irritant doses of HQ, RA and sodium lauryl sulphate (SLS) to cultures of keratinocytes and/or melanocytes. In this study, the role of S100B on melanocyte viability and cytotoxicity was examined. S100B was detected in melanocytes, but not in keratinocytes or fibroblasts. Melanocytes after treatment with increasing concentrations of HQ, RA, SLS and urushiol showed significant increases in intracellular and extracellular S100B expression with reduced viable cell number and increased release of lactate dehydrogenase. No RAGE expression and no significant function of CD166/ALCAM in melanocyte survival and cytotoxicity favoured the role of intracellular S100B in chemically irritated melanocytes. S100B knock-down increased apoptosis through inhibition of PI3K/AKT, NF-κB and ERK activation, suggesting the increased intracellular S100B expression by chemical irritation as a compensatory reaction to reduce cytotoxicity. The numerical decrease in S100B/c-kit-double-positive melanocytes was also examined in human skin epidermis irritated by HQ or RA with stronger staining intensities of S100B. Collectively, the decrease in viable cell number by reduced intracellular S100B levels in vitro and by chemical irritation in vivo suggests that S100B could be a potential biomarker for melanocytes cytotoxicity.
Department of Dermatology, Graduate School of Medicine, Dongguk University Seoul, Gyeonggi-do, South Korea.
Kyung Ah
KA
Cheong
Minsoo
M
Noh
Chang-Hyun
CH
Kim
Ai-Young
AY
Lee
D000328:Adult; D015703:Antigens, CD / Q000378:metabolism; D017209:Apoptosis / Q000235:genetics; D015415:Biomarkers / Q000378:metabolism; D002396:Catechols / Q000494:pharmacology; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects*; D002478:Cells, Cultured; D003879:Dermatologic Agents / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D005326:Fetal Proteins / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006801:Humans; D006873:Hydroquinones / Q000494:pharmacology; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D008544:Melanocytes / Q000187:drug effects* / Q000378:metabolism*; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism; D064568:S100 Calcium Binding Protein beta Subunit / Q000235:genetics / Q000378:metabolism*; D012867:Skin / Q000187:drug effects / Q000378:metabolism*; D012967:Sodium Dodecyl Sulfate / Q000494:pharmacology; D014212:Tretinoin / Q000494:pharmacology; D020410:Activated-Leukocyte Cell Adhesion Molecule
D015703:Antigens, CD; D015415:Biomarkers; D002396:Catechols; D015816:Cell Adhesion Molecules, Neuronal; D003879:Dermatologic Agents; D048049:Extracellular Signal-Regulated MAP Kinases; D005326:Fetal Proteins; D006873:Hydroquinones; D007770:L-Lactate Dehydrogenase; D016328:NF-kappa B; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D019009:Proto-Oncogene Proteins c-kit; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D064568:S100 Calcium Binding Protein beta Subunit; D012967:Sodium Dodecyl Sulfate; D014212:Tretinoin; C105613:ALCAM protein, human; D020410:Activated-Leukocyte Cell Adhesion Molecule; C579160:S100B protein, human; C003747:urushiol; C031927:hydroquinone
S100B; cytotoxicity; melanocyte; potential biomarker; viability