Abstract：
:Nuclear factor kappa B (NF(kappa)B) transcription factor plays a key role in the expression of many genes involved in the inflammatory process. We used the Freund's Complete Adjuvant (FCA)-induced model of peripheral inflammation to investigate the anti-inflammatory effects of double stranded oligodeoxynucleotides (ODN) with consensus NF(kappa)B sequence as transcription factor decoys to inhibit NF(kappa)kappaB activation in the dorsal root ganglia (DRG). Local administration of the wild-type-, but not mutant-ODN decoy, dose-dependently inhibited edema formation and paw withdrawal latency as a measure of hyperalgesic response induced by FCA in rat paw. Biochemical assays performed in ipsilateral L4/L5 dorsal root ganglia obtained following FCA/wild-type ODN treatment showed: (1) an inhibition of the activity of c-Src kinase, a member of the non-receptor tyrosine kinase super family, (2) a decreased level of p65 NF(kappa)B subunit, and (3) an inhibition of cyclooxygenase-2 (COX-2) protein expression, a major pro-inflammatory enzyme transcriptionally controlled by NF(kappa)B. The present results indicate that the wild-type ODN decoy may act as a competitor for NF(kappa)B binding to its cognate recognition sequence as well as a modulator of c-Src activity in the DRG. The NF(kappa)B/c-Src interaction may represent a novel pathway for further exploring the molecular mechanism of inflammatory pain.
journal_name
Neurosci Lettjournal_title
Neuroscience lettersauthors
Igwe OJdoi
10.1016/j.neulet.2005.02.020keywords:
subject
Has Abstractpub_date
2005-06-10 00:00:00pages
114-9issue
1-2eissn
0304-3940issn
1872-7972pii
S0304-3940(05)00197-7journal_volume
381pub_type
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