Oligonucleotides suppress PKB/Akt and act as superinductors of apoptosis in human keratinocytes

Stefan Kippenberger*, Jutta Müller, Maike Schultz, Annette Dorn, Andreas Bock, Hüseyin Aygün, Diamant Thaçi, Matthias Hofmann, Roland Kaufmann, August Bernd

*Corresponding author for this work
3 Citations (Scopus)


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.

Original languageEnglish
JournalNucleic Acids Research
Issue number12
Pages (from-to)3850-3864
Number of pages15
Publication statusPublished - 2009

Research Areas and Centers

  • Academic Focus: Center for Infection and Inflammation Research (ZIEL)


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