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Selective inhibition of cyclooxygenase-2 with antisense oligodeoxynucleotide restricts induction of rat
1First Department of Internal Medicine, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto, 602-8566, Japan.
Abstract:
The effects of cyclooxygenase (COX)-2 antisense oligodeoxynucleotide (ODN) in induction of adjuvant-induced arthritis were investigated. Female Lewis rats were injected with Mycobacterium butyricum intradermally at the base of tails to induce arthritis. Synthetic 18 mer phosphorothioate ODNs corresponding to the translation initiation site of rat COX-2 mRNA were prepared. The antisense (AS), sense (S), and "scrambled" (Sc) ODNs were intraperitoneally administered. Arthropathy was evaluated with arthritis score, paw edema, and histological examination. Expression of COX-1 and -2 protein and mRNA were examined with immunostaining and reverse-transcription polymerase chain reaction, respectively. COX-2 AS ODN significantly suppressed induction of arthritis in a dose-dependent manner without severe adverse effects, whereas S and Sc ODNs did not show significant inhibitory effects. COX-2 mRNA and protein expression were also suppressed only by COX-2 AS ODN without any alteration of COX-1 expression. These data suggest that selective inhibition of COX-2 with AS ODN may have a therapeutic potency in the treatment of rheumatoid arthritis.
Insights
Selective inhibition of cyclooxygenase (COX)-2 using antisense oligodeoxynucleotide (ODN) effectively suppressed adjuvant-induced arthritis in rats. This targeted approach shows therapeutic potential for rheumatoid arthritis treatment.
Area of Science:
- Biomedical Science
- Pharmacology
- Immunology
Background:
- Adjuvant-induced arthritis is a model for rheumatoid arthritis.
- Cyclooxygenase-2 (COX-2) plays a key role in inflammatory processes.
- Targeting COX-2 offers a potential therapeutic strategy for arthritis.
Purpose of the Study:
- To investigate the efficacy of cyclooxygenase (COX)-2 antisense oligodeoxynucleotide (ODN) in suppressing adjuvant-induced arthritis.
- To evaluate the safety and specificity of COX-2 AS ODN treatment.
- To explore the therapeutic potential of selective COX-2 inhibition for rheumatoid arthritis.
Main Methods:
- Induction of arthritis in Lewis rats using Mycobacterium butyricum.
- Administration of synthetic 18-mer phosphorothioate ODNs (antisense, sense, scrambled) targeting rat COX-2 mRNA.
- Assessment of arthropathy via arthritis score, paw edema, and histological analysis.
- Examination of COX-1 and COX-2 protein and mRNA expression using immunostaining and RT-PCR.
Main Results:
- COX-2 antisense ODN significantly suppressed arthritis induction in a dose-dependent manner.
- Sense and scrambled ODNs showed no significant inhibitory effects on arthritis.
- COX-2 AS ODN reduced COX-2 mRNA and protein expression without affecting COX-1.
- No severe adverse effects were observed with COX-2 AS ODN treatment.
Conclusions:
- Selective inhibition of COX-2 with antisense ODN is effective in suppressing adjuvant-induced arthritis.
- COX-2 AS ODN demonstrates therapeutic potential for rheumatoid arthritis.
- This targeted approach offers a promising strategy for managing inflammatory arthritis.