TY  - JOUR
A1  - Panayotova-Dimitrova, Diana
A1  - Feoktistova, Maria
A1  - Ploesser, Michaela
A1  - Kellert, Beate
A1  - Hupe, Mike
A1  - Horn, Sebastian
A1  - Makarov, Roman
A1  - Jensen, Federico
A1  - Porubsky, Stefan
A1  - Schmieder, Astrid
A1  - Zenclussen, Ana Claudia
A1  - Marx, Alexander
A1  - Kerstan, Andreas
A1  - Geserick, Peter
A1  - He, You-Wen
A1  - Leverkus, Martin
T1  - cFLIP Regulates Skin Homeostasis and Protects against TNF-Induced Keratinocyte Apoptosis
JF  - Cell Reports
N2  - 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 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.
KW  - eczematous dermatitis
KW  - programmed necrosis
KW  - gene induction
KW  - in-vivo
KW  - activation
KW  - mediated apoptosis
KW  - c-flip
KW  - cell-death
KW  - Stevens-Johnson syndrome
KW  - toxic epidermal necrolysis
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-122155
VL  - 5
ER  -