title: Preferential secretion of inducible HSP70 by vitiligo melanocytes under stress.
abstract: Inducible HSP70 (HSP70i) chaperones peptides from stressed cells, protecting them from apoptosis. Upon extracellular release, HSP70i serves an adjuvant function, enhancing immune responses to bound peptides. We questioned whether HSP70i differentially protects control and vitiligo melanocytes from stress and subsequent immune responses. We compared expression of HSP70i in skin samples, evaluated the viability of primary vitiligo and control melanocytes exposed to bleaching phenols, and measured secreted HSP70i. We determined whether HSP70i traffics to melanosomes to contact immunogenic proteins by cell fractionation, western blotting, electron microscopy, and confocal microscopy. Viability of vitiligo and control melanocytes was equally affected under stress. However, vitiligo melanocytes secreted increased amounts of HSP70i in response to MBEH, corroborating with aberrant HSP70i expression in patient skin. Intracellular HSP70i colocalized with melanosomes, and more so in response to MBEH in vitiligo melanocytes. Thus, whereas either agent is cytotoxic to melanocytes, MBEH preferentially induces immune responses to melanocytes.
authors.affiliation: Departments of Pathology and Microbiology & Immunology/Cardinal Bernardin Cancer Center, Loyola University Chicago, Maywood, IL, USA.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Mosenson
authors.forename: Kelsey
authors.initials: K
authors.lastname: Flood
authors.forename: Jared
authors.initials: J
authors.lastname: Klarquist
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Eby
authors.forename: Amy
authors.initials: A
authors.lastname: Koshoffer
authors.forename: Raymond E
authors.initials: RE
authors.lastname: Boissy
authors.forename: Andreas
authors.initials: A
authors.lastname: Overbeck
authors.forename: Rebecca C
authors.initials: RC
authors.lastname: Tung
authors.forename: I Caroline
authors.initials: IC
authors.lastname: Le Poole
mesh_terms: D000293:Adolescent; D000328:Adult; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D006873:Hydroquinones / Q000494:pharmacology; D007231:Infant, Newborn; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008544:Melanocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D020460:Melanosomes / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D008875:Middle Aged; D010636:Phenols / Q000494:pharmacology; D021381:Protein Transport / Q000187:drug effects; D012867:Skin / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013312:Stress, Physiological / Q000187:drug effects; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism; D014820:Vitiligo / Q000378:metabolism* / Q000473:pathology; D055815:Young Adult
chemical_list: D018840:HSP70 Heat-Shock Proteins; D006873:Hydroquinones; D010636:Phenols; C006429:monobenzone; C006862:butylphen
keywords: autoimmune; heat shock protein; melanocyte; stress; vitiligo