cFLIP Regulates Skin Homeostasis and Protects against TNF-Induced Keratinocyte Apoptosis
Zitieren Sie bitte immer diese URN: urn:nbn:de:bvb:20-opus-122155
- FADD, caspase-8, and cFLIP regulate the outcome of cell death signaling. Mice that constitutively lack these molecules die at an early embryonic age, whereas tissue-specific constitutive deletion of FADD or caspase-8 results in inflammatory skin disease caused by increased necroptosis. The function of cFLIP in the skin in vivo is unknown. In contrast to tissue-specific caspase-8 knockout, we show that mice constitutively lacking cFLIP in the epidermis die around embryonic days 10 and 11. When cFLIP expression was abrogated in adult skin ofFADD, caspase-8, and cFLIP regulate the outcome of cell death signaling. Mice that constitutively lack these molecules die at an early embryonic age, whereas tissue-specific constitutive deletion of FADD or caspase-8 results in inflammatory skin disease caused by increased necroptosis. The function of cFLIP in the skin in vivo is unknown. In contrast to tissue-specific caspase-8 knockout, we show that mice constitutively lacking cFLIP in the epidermis die around embryonic days 10 and 11. When cFLIP expression was abrogated in adult skin of cFLIP(fl/fl)-K14CreER(tam) mice, severe inflammation of the skin with concomitant caspase activation and apoptotic, but not necroptotic, cell death developed. Apoptosis was dependent of autocrine tumor necrosis factor production triggered by loss of cFLIP. In addition, epidermal cFLIP protein was lost in patients with severe drug reactions associated with epidermal apoptosis. Our data demonstrate the importance of cFLIP for the integrity of the epidermis and for silencing of spontaneous skin inflammation.…
Autor(en): | Diana Panayotova-Dimitrova, Maria Feoktistova, Michaela Ploesser, Beate Kellert, Mike Hupe, Sebastian Horn, Roman Makarov, Federico Jensen, Stefan Porubsky, Astrid Schmieder, Ana Claudia Zenclussen, Alexander Marx, Andreas Kerstan, Peter Geserick, You-Wen He, Martin Leverkus |
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URN: | urn:nbn:de:bvb:20-opus-122155 |
Dokumentart: | Artikel / Aufsatz in einer Zeitschrift |
Institute der Universität: | Medizinische Fakultät / Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie |
Sprache der Veröffentlichung: | Englisch |
Titel des übergeordneten Werkes / der Zeitschrift (Englisch): | Cell Reports |
Erscheinungsjahr: | 2013 |
Band / Jahrgang: | 5 |
Seitenangabe: | 397-408 |
Originalveröffentlichung / Quelle: | Cell Reports 5, 397–408, October 31, 2013. DOI:10.1016/j.celrep.2013.09.035 |
DOI: | https://doi.org/10.1016/j.celrep.2013.09.035 |
Allgemeine fachliche Zuordnung (DDC-Klassifikation): | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 614 Inzidenz und Prävention von Krankheiten |
Freie Schlagwort(e): | Stevens-Johnson syndrome; activation; c-flip; cell-death; eczematous dermatitis; gene induction; in-vivo; mediated apoptosis; programmed necrosis; toxic epidermal necrolysis |
Datum der Freischaltung: | 24.02.2016 |
Lizenz (Deutsch): | CC BY-NC-ND: Creative-Commons-Lizenz: Namensnennung, Nicht kommerziell, Keine Bearbeitung |