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Cathepsin S activity is detectable in human keratinocytes and is selectively upregulated upon stimulation with interferon-gamma

Schwarz, Gerold
Braun, Manuela
Schroter, Christian J.
Burster, Timo
Flad, Thomas
Dressel, Daniela
Weber, Ekkehard
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Published in Journal of investigative dermatology. 2002, vol. 119, no. 1, p. 44-49
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.
Keywords Antigen Presentation/physiologyAntineoplastic Agents/*pharmacologyB-Lymphocytes/enzymologyCathepsin B/metabolismCathepsin LCathepsins/*metabolismCell Line, TransformedCysteine EndopeptidasesEnzyme Activation/drug effectsFlow CytometryHumansInterferon-gamma/*pharmacologyKeratinocytes/cytology/*enzymologyLysosomes/enzymologyPsoriasis/immunology/metabolismUp-Regulation/drug effects
PMID: 12164923
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SCHWARZ, Gerold et al. Cathepsin S activity is detectable in human keratinocytes and is selectively upregulated upon stimulation with interferon-gamma. In: Journal of investigative dermatology, 2002, vol. 119, n° 1, p. 44-49. doi: 10.1046/j.1523-1747.2002.01800.x

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Deposited on : 2013-09-20

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