Effect of Transcription Factor Decoy for NF-κB on the TNF-α Induced Cytokine and ICAM-1 Expression in Cultured HaCaT cells
Annals of Dermatology
;
: 93-98, 2003.
Article
in English
| WPRIM
| ID: wpr-100506
ABSTRACT
BACKGROUND:
Psoriasis is the most prevalent T-cell-mediated inflammatory skin disease in humans. Numerous cytokines and adhesion molecules are expressed in the skin lesion of psoriasis such as TNF-α, IL-1, IL-6, VCAM-1 and ICAM-1. All of them contain at least one binding site for the transcription factor NF-κB. TNF-α activates NF-κB and many other transcription factors. Thus, transcription and expression of many genes involved in the inflammatory process may be influenced by TNF-α.OBJECTIVE:
The purpose of this study was to study the effect of synthetic double-stranded DNA with high affinity for the NF-κB binding site on the TNF-α induced proinflammatory cytokines and ICAM-1 gene expression in the HaCaT cells. MATERIAL ANDMETHODS:
We examined whether inhibition of NF-κB activity by oligodeoxynucleotides (ODN) decoy for NF-κB blocks TNF-α induced cytokines such as IL-la, IL-1 a, IL-6 and ICAM-1 expression with electrophoretic mobility shift assay (EMSA) and reverse transcription-polymerase chain reaction (RT-PCR).RESULTS:
In EMSA, TNF-α treatment (10 ng/ml) induced the activation of NF-κB. The NF-κB binding activity in the TNF-α treated HaCaT cells increased 5.0-fold compared to non-treated group. Next, we examined the effect of liposome mediated NF-κB decoy oligonucleotides (ODN) transfection. After transfection of the NF-κB decoy ODN, TNF-α increased NF-κB binding activity to 1.9-fold of non-treated group. Accordingly the transfection of NF-κB decoy ODN inhibited the TNF-α induced NF-κB binding activity up to 63%. RT-PCR analysis revealed that the transfection of NF-κB decoy ODN inhibited TNF-α induced cytokines and ICAM-1 mRNA expression.CONCLUSION:
Taken together, our results suggest the potential utility of NF-κB decoy technique for biologic therapy of psoriasis.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Oligodeoxyribonucleotides
/
Oligonucleotides
/
Psoriasis
/
Skin
/
Skin Diseases
/
Transcription Factors
/
Binding Sites
/
Biological Therapy
/
In Vitro Techniques
/
DNA
Limits:
Humans
Language:
English
Journal:
Annals of Dermatology
Year:
2003
Type:
Article
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