TY  - JOUR
A1  - Kippenberger, Stefan
A1  - Müller, Jutta
A1  - Schultz, Maike
A1  - Dorn, Annette
A1  - Bock, Andreas
A1  - Aygün, Hüseyin
A1  - Thaçi, Diamant
A1  - Hofmann, Matthias
A1  - Kaufmann, Roland
A1  - Bernd, August
T1  - Oligonucleotides suppress PKB/Akt and act as superinductors of apoptosis in human keratinocytes
T2  - Nucleic acids research
N2  - DNA oligonucleotides (ODN) applied to an organism are known to modulate the innate and adaptive immune system. Previous studies showed that a CpG-containing ODN (CpG-1-PTO) and interestingly, also a non-CpG-containing ODN (nCpG- 5-PTO) suppress inflammatory markers in skin. In the present study it was investigated whether these molecules also influence cell apoptosis. Here we show that CpG-1-PTO, nCpG-5-PTO, and also natural DNA suppress the phosphorylation of PKB/Akt in a cell-type-specific manner. Interestingly, only epithelial cells of the skin (normal human keratinocytes, HaCaT and A-431) show a suppression of PKB/Akt. This suppressive effect depends from ODN lengths, sequence and backbone. Moreover, it was found that TGFa-induced levels of PKB/Akt and EGFR were suppressed by the ODN tested. We hypothesize that this suppression might facilitate programmed cell death. By testing this hypothesis we found an increase of apoptosis markers (caspase 3/7, 8, 9, cytosolic cytochrome c, histone associated DNA fragments, apoptotic bodies) when cells were treated with ODN in combination with low doses of staurosporin, a wellknown pro-apoptotic stimulus. In summary the present data demonstrate DNA as a modulator of apoptosis which specifically targets skin epithelial cells.
Y1  - 2009
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/6599
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30-66889
SN  - 1362-4962
SN  - 0305-1048
N1  - © 2009 The Author(s). This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/
by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
VL  - 37
IS  - 12
SP  - 3850
EP  - 3864
PB  - Oxford Univ. Press
CY  - Oxford
ER  -