title: Human keratinocytes release high levels of inducible heat shock protein 70 that enhances peptide uptake.
abstract: BACKGROUND
  The stress-inducible chaperone heat shock protein (HSP) 70 is considered a 'danger signal' if released into the extracellular environment. It has been proposed to play a role in the pathogenesis of skin diseases such as psoriasis and lupus erythematosus (LE).
  
  
  OBJECTIVE
  The aim of this study was to decipher the role of human primary keratinocytes with regard to release and reactivity to HSP70.
  
  
  METHODS
  We determined HSP70 and IFNγ in cell supernatants by ELISA. Uptake of labelled HSP70 or labelled peptide by human primary keratinocytes or macrophages was analysed by flow cytometry and fluorescent microscopy.
  
  
  RESULTS
  We found that living keratinocytes are an important source of HSP70 in the skin compartment. They release considerably more HSP70 than fibroblasts, macrophages or lymphocytes. Interestingly, keratinocytes also bind and internalise HSP70/HSP70-peptide complexes. TNFα, IL-27 as well as HMGB-1 enhanced the uptake of HSP70. No difference with regard to HSP70 release or uptake was observable between keratinocytes from healthy donors or patients with cutaneous LE. Keratinocytes pulsed with HSP70-peptide complexes significantly increased IFNγ production by autologous T cells.
  
  
  CONCLUSIONS
  Production and uptake of inducible HSP70 by keratinocytes may critically influence the chronic course of inflammatory skin diseases.
authors.affiliation: Division of Immunodermatology and Allergy Research, Department of Dermatology and Allergy, Hannover Medical School, Hannover, Germany.
authors.forename: Dong
authors.initials: D
authors.lastname: Wang
authors.forename: Britta
authors.initials: B
authors.lastname: Eiz-Vesper
authors.forename: Jana
authors.initials: J
authors.lastname: Zeitvogel
authors.forename: Ralf
authors.initials: R
authors.lastname: Dressel
authors.forename: Thomas
authors.initials: T
authors.lastname: Werfel
authors.forename: Miriam
authors.initials: M
authors.lastname: Wittmann
mesh_terms: D001706:Biopsy; D016022:Case-Control Studies; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008178:Lupus Erythematosus, Cutaneous / Q000378:metabolism* / Q000473:pathology; D010455:Peptides / Q000378:metabolism*; D012867:Skin / Q000378:metabolism / Q000473:pathology
chemical_list: D016207:Cytokines; D018840:HSP70 Heat-Shock Proteins; D010455:Peptides; D007371:Interferon-gamma