UV irradiation of human keratinocytes activates the inflammasome

Details

Serval ID
serval:BIB_E2F9A1B36352
Type
Inproceedings: an article in a conference proceedings.
Publication sub-type
Abstract (Abstract): shot summary in a article that contain essentials elements presented during a scientific conference, lecture or from a poster.
Collection
Publications
Institution
Title
UV irradiation of human keratinocytes activates the inflammasome
Title of the conference
37th Annual Meeting of the European Society Dermatological Research
Author(s)
Beer H. D., Feldmeyer L., Keller M., Hohl D., Werner S.
Address
Zurich, Switzerland, Sep 05-08, 2007
ISBN
0022-202X
Publication state
Published
Issued date
2008
Peer-reviewed
Oui
Volume
127
Series
Journal of Investigative Dermatology
Pages
S68-S68
Language
english
Abstract
Human keratinocytes represent a potent source of the pro-inflammatory cytokines pro-interleukin(IL)-1α and -β. ProIL-1β requires processing by caspase-1 (IL-1β-converting enzyme, ICE) for activation and receptor binding. ProIL-1α and -β lack a signal peptide and leave the cell via the alternative secretion pathway, which is independent of the classical ER/Golgi pathway. Both cytokines are stored in the cytoplasm and can be activated and released upon UV irradiation. In macrophages maturation of proIL-1β requires the activation of inflammasomes, innate multiprotein immune complexes, which are essential for the activation of caspase-1 and thereby for processing of proIL-1β. However, the intracellular pathways, which are responsible for activation of proIL-1β and secretion of IL-1β in keratinocytes, are unknown. We show that human keratinocytes express inflammasome proteins in vitro and in vivo. UVB irradiation of keratinocytes results in an increase of cytoplasmic Ca2+ from intracellular stores. This shift is required for inflammasome-dependent activation of caspase-1 and subsequent processing of proIL-1β and secretion of IL-1β. In contrast to macrophages, caspase-1 cannot activate proIL-18 in keratinocytes, although secretion of this cytokine is also induced by UVB irradiation. In vivo, caspase-1 is also essential for UVB-induced inflammation in the skin, since caspase-1 knockout mice showed a strongly reduced inflammatory response after UVB irradiation. Our results suggest that keratinocytes are important immuno-competent cells under physiological and pathological conditions.
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Create date
29/09/2009 15:30
Last modification date
20/08/2019 16:06
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