TY - JOUR
T1 - Oligonucleotides suppress PKB/Akt and act as superinductors of apoptosis in human keratinocytes
AU - Kippenberger, Stefan
AU - Müller, Jutta
AU - Schultz, Maike
AU - Dorn, Annette
AU - Bock, Andreas
AU - Aygün, Hüseyin
AU - Thaçi, Diamant
AU - Hofmann, Matthias
AU - Kaufmann, Roland
AU - Bernd, August
N1 - Funding Information:
Federal Ministry of Education and Research (BMBF), Germany (BioChancePLUS, Number 0313642B).
PY - 2009
Y1 - 2009
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 TGFα-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 well-known pro-apoptotic stimulus. In summary the present data demonstrate DNA as a modulator of apoptosis which specifically targets skin epithelial cells.
AB - 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 TGFα-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 well-known pro-apoptotic stimulus. In summary the present data demonstrate DNA as a modulator of apoptosis which specifically targets skin epithelial cells.
UR - http://www.scopus.com/inward/record.url?scp=67651159061&partnerID=8YFLogxK
U2 - 10.1093/nar/gkp252
DO - 10.1093/nar/gkp252
M3 - Journal articles
C2 - 19386618
AN - SCOPUS:67651159061
SN - 0305-1048
VL - 37
SP - 3850
EP - 3864
JO - Nucleic Acids Research
JF - Nucleic Acids Research
IS - 12
ER -