Enhancement of ultraviolet-induced apoptosis by NF-kappaB decoy oligonucleotides
S Yokoyama1, H Nakano, T Yamazaki
1Department of Dermatology, Hirosaki University School of Medicine, 5 Zaifu-cho, Hirosaki 036-8562, Japan.
Background:
A decoy strategy utilizing oligonucleotides (ODN) containing the specific binding sequence of a certain transcription factor has been developed and is considered to be a potential new class of antigene therapy. However, the application of this new therapeutic modality to skin diseases has not been fully documented.
Objectives:
The aim of this work was to examine the effects of the nuclear factor (NF)-kappaB decoy ODN on UV-elicited skin change.
Methods:
Mouse keratinocyte Pam 212 cells were transfected with NF-kappaB decoy ODN to examine the effects of the decoy ODN on ultraviolet (UV) B-induced apoptosis. Tape-stripped rat dorsal skin was treated with an ointment containing NF-kappaB decoy ODN for the examination of the in vivo impact of the decoy ODN on sunburned cell (SBC) formation and UVB erythema.
Results:
NF-kappaB decoy ODN specifically induced apoptosis of Pam 212 cells and SBC formation was significantly enhanced by topical NF-kappaB decoy ODN ointment, while UV-induced erythema was not affected.
Conclusions:
These data suggest that enhancement of UV-induced apoptosis by NF-kappaB decoy ODN may play a cancer-preventive role by further eliminating photodamaged keratinocytes.
Insights
Nuclear factor (NF)-kappaB decoy oligonucleotides (ODN) promote apoptosis in skin cells. Topical NF-kappaB decoy ODN enhanced sunburned cell formation, suggesting a potential role in preventing skin cancer by eliminating photodamaged cells.
Area of Science:
- Dermatology
- Molecular Biology
- Cancer Prevention
Background:
- Oligonucleotides (ODN) as decoy agents targeting transcription factors represent a novel antigene therapy.
- The therapeutic potential of decoy ODN in skin diseases remains underexplored.
Purpose of the Study:
- To investigate the impact of nuclear factor (NF)-kappaB decoy ODN on ultraviolet (UV) radiation-induced skin alterations.
- To assess the effects of NF-kappaB decoy ODN on UV-B-induced apoptosis in keratinocytes and in vivo skin responses.
Main Methods:
- In vitro transfection of mouse keratinocyte Pam 212 cells with NF-kappaB decoy ODN to evaluate UVB-induced apoptosis.
- In vivo topical application of NF-kappaB decoy ODN ointment on tape-stripped rat dorsal skin to assess sunburned cell (SBC) formation and erythema after UVB exposure.
Main Results:
- NF-kappaB decoy ODN treatment specifically induced apoptosis in Pam 212 keratinocytes.
- Topical application of NF-kappaB decoy ODN ointment significantly increased SBC formation.
- UVB-induced erythema in the skin was not significantly affected by the NF-kappaB decoy ODN ointment.
Conclusions:
- Enhanced UV-induced apoptosis by NF-kappaB decoy ODN suggests a potential cancer-preventive mechanism.
- This strategy may aid in eliminating photodamaged keratinocytes, thereby reducing the risk of skin cancer.
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