Transcription factor decoy oligodeoxynucleotides to nuclear factor-κB inhibit reverse passive Arthus reaction in rat

D'Acquisto, F., Ianaro, A., Ialenti, A., Maffia, P. , Maiuri, M. and Carnuccio, R. (2001) Transcription factor decoy oligodeoxynucleotides to nuclear factor-κB inhibit reverse passive Arthus reaction in rat. Naunyn-Schmiedeberg's Archives of Pharmacology, 364(5), pp. 422-429. (doi:10.1007/s002100100472) (PMID:11692225)

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Abstract

In the present study we investigated in the reverse passive Arthus reaction elicited in the rat skin the anti-inflammatory effect of double-stranded oligodeoxynucleotides (ODN) with consensus nuclear factor-κB (NF-κB) sequence as transcription factor decoys (TFD) to inhibit NF-κB binding to native DNA sites. Local administration of wild-type-, but not mutant-decoy ODN, dose-dependently reduced both plasma leakage and neutrophil infiltration in rat skin. Molecular analysis performed on soft tissue obtained from rat skin demonstrated: (1) an inhibition of NF-κB/DNA binding activity; (2) a decreased nuclear level of p50 and p65 NF-κB subunits; (3) an inhibition of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) protein expression, two inflammatory enzymes transcriptionally controlled by NF-κB. Furthermore, SN-50, a cell-permeable peptide capable of inhibiting the nuclear translocation of NF-κB complexes, as well as ammonium pyrrolidine dithiocarbamate, an inhibitor of NF-κB activation, exhibited a similar profile of activity of decoy ODN. Our results indicate that decoy ODN, acting as an in vivo competitor for the transcription factor's ability to bind to cognate recognition sequence, may represent a novel strategy to modulate immune reactions.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Maffia, Dr Pasquale
Authors: D'Acquisto, F., Ianaro, A., Ialenti, A., Maffia, P., Maiuri, M., and Carnuccio, R.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Naunyn-Schmiedeberg's Archives of Pharmacology
Publisher:Springer-Verlag
ISSN:0028-1298
ISSN (Online):1432-1912

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