title: Cathepsin S activity is detectable in human keratinocytes and is selectively upregulated upon stimulation with interferon-gamma.
abstract: Keratinocytes are an integral component of the skin immune system and function as nonprofessional antigen-presenting cells in pathophysiologic conditions when they express major histocompatibility complex class II molecules, e.g., in psoriasis. In order to analyze further this function we investigated the activity of cathepsin S in comparison with cathepsins B and L. These enzymes were suggested to be involved in antigen presentation. Specific catalytic activities of these cathepsins were determined fluorometrically by hydrolysis of a synthetic substrate (Z-Phe-Arg-7-amido-4-methylcoumarin) in subcellular fractions of human keratinocytes. It was found that the human keratinocyte cell line HaCaT exhibits activities of all three cathepsins investigated. Endosomal/lysosomal compartments show highest cathepsin activities. Normal human keratinocytes in primary culture show a comparable pattern of cathepsin activities. In contrast to this, in syngeneic Epstein-Barr virus-transformed B cells the level of cathepsin B activity was found to be 10% of that in the corresponding keratinocytes, whereas the activities for cathepsins L and S were in a similar range. Interferon-gamma stimulation of primary keratinocytes and HaCaT cells resulted in a selective upregulation of the cathepsin S activity, the extent of which was very similar. The mechanism of this upregulation was demonstrated as induction at the mRNA and protein levels. This report documents that cathepsin S in human keratinocytes is selectively upregulated, in parallel to major histocompatibility complex class II molecules, in response to a pro-inflammatory cytokine. Our observations support the concept of keratinocytes functioning as nonprofessional antigen-presenting cells in states of inflammation.
authors.affiliation: Medical and Natural Sciences Research Center, University of Tübingen, Ob dem Himmelreich 7, D-72074 Tübingen, Germany.
authors.forename: Gerold
authors.initials: G
authors.lastname: Schwarz
authors.forename: Wolf-Henning
authors.initials: WH
authors.lastname: Boehncke
authors.forename: Manuela
authors.initials: M
authors.lastname: Braun
authors.forename: Christian J
authors.initials: CJ
authors.lastname: Schröter
authors.forename: Timo
authors.initials: T
authors.lastname: Burster
authors.forename: Thomas
authors.initials: T
authors.lastname: Flad
authors.forename: Daniela
authors.initials: D
authors.lastname: Dressel
authors.forename: Ekkehard
authors.initials: E
authors.lastname: Weber
authors.forename: Heide
authors.initials: H
authors.lastname: Schmid
authors.forename: Hubert
authors.initials: H
authors.lastname: Kalbacher
mesh_terms: D017951:Antigen Presentation / Q000502:physiology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001402:B-Lymphocytes / Q000201:enzymology; D002401:Cathepsin B / Q000378:metabolism; D056668:Cathepsin L; D002403:Cathepsins / Q000378:metabolism*; D002461:Cell Line, Transformed; D003546:Cysteine Endopeptidases; D004789:Enzyme Activation / Q000187:drug effects; D005434:Flow Cytometry; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D015603:Keratinocytes / Q000166:cytology / Q000201:enzymology*; D008247:Lysosomes / Q000201:enzymology; D011565:Psoriasis / Q000276:immunology / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D007371:Interferon-gamma; D002403:Cathepsins; D003546:Cysteine Endopeptidases; D002401:Cathepsin B; C534281:CTSL protein, human; D056668:Cathepsin L; C028217:cathepsin S