Selective inhibition of cyclooxygenase-2 with antisense oligodeoxynucleotide restricts induction of rat adjuvant-induced arthritis
| Autor: | Yutaka Kawahito, Akira Hashiramoto, Yasunori Tsubouchi, Miki Inoue, Timothy Hla, Akiko Komatsu, Ryoji Yamada, Shigehiko Mukai, Ken-ichiro Inoue, Hajime Sano, Masataka Kohno, Motoharu Kondo |
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| Rok vydání: | 2000 |
| Předmět: |
Biophysics
Arthritis Biochemistry Sense (molecular biology) Arthropathy medicine Potency Animals Humans Cyclooxygenase Inhibitors RNA Messenger Molecular Biology DNA Primers Messenger RNA biology Base Sequence Cyclooxygenase 2 Inhibitors Chemistry Membrane Proteins hemic and immune systems Cell Biology respiratory system Oligonucleotides Antisense medicine.disease Molecular biology Arthritis Experimental Rats Isoenzymes Cyclooxygenase 2 Prostaglandin-Endoperoxide Synthases Rats Inbred Lew Rheumatoid arthritis biology.protein Cyclooxygenase 1 Female Cyclooxygenase Ankle Immunostaining |
| Zdroj: | Biochemical and biophysical research communications. 269(2) |
| ISSN: | 0006-291X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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