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

  • 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.
Metadaten
Author:Stefan KippenbergerORCiDGND, Jutta Müller, Maike Schultz, Annette Dorn, Andreas Bock, Hüseyin Aygün, Diamant ThaçiORCiD, Matthias HofmannGND, Roland KaufmannGND, August BerndORCiDGND
URN:urn:nbn:de:hebis:30-66889
DOI:https://doi.org/10.1093/nar/gkp252
ISSN:1362-4962
ISSN:0305-1048
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/19386618
Parent Title (English):Nucleic acids research
Publisher:Oxford Univ. Press
Place of publication:Oxford
Document Type:Article
Language:English
Date of Publication (online):2009/06/17
Date of first Publication:2009/04/22
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2009/06/17
Volume:37
Issue:12
Page Number:15
First Page:3850
Last Page:3864
Note:
© 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.
Source:Nucleic Acids Research, 2009, 1–15 ; doi:10.1093/nar/gkp252
HeBIS-PPN:214272494
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung-Nicht kommerziell 2.0