The new antirheumatic drug KE-298 suppresses monocyte chemoattractant protein (MCP)-1 and RANTES production in rats with adjuvant-induced arthritis and in IL-1beta-stimulated synoviocytes of patients with rheumatoid arthritis.
We analyzed the effects of the new antirheumatic drug KE-298 on monocyte chemoattractant protein (MCP)-1 and regulated on activation normal T-cell expressed and secreted (RANTES) production in rats with adjuvant-induced arthritis and in interleukin (IL)-1beta-stimulated rheumatoid arthritis (RA) synoviocytes. In rats with adjuvant-induced arthritis, the enhanced production of MCP-1 and RANTES and the development of arthritis were suppressed by oral treatment with 100 mg/kg per day of KE-298 for 18 days. Furthermore, KE-298 (10-100 microg/ml) suppressed MCP-1 and RANTES production by IL-1beta-stimulated RA synoviocytes through inhibition of NF-kappaB and AP-1 activation. These results suggest that the inhibitory effect of KE-298 on MCP-1 and RANTES production might partly explain its efficacy in rats with adjuvant-induced arthritis and in patients with RA.
Inoue
T
T
Institute of Medical Science, St Marianna University School of Medicine, Kawasaki, Kanagawa, Japan. s15376@ccm.taisho.co.jp
Yamashita
M
M
Higaki
M
M
D000368:Aged; D000818:Animals; D018501:Antirheumatic Agents / Q000494:pharmacology*; D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000188:drug therapy*; D001483:Base Sequence; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism*; D018946:Chemokine CCL5 / Q000096:biosynthesis*; D004195:Disease Models, Animal; D004586:Electrophoresis; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010666:Phenylpropionates / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012680:Sensitivity and Specificity; D013583:Synovial Membrane / Q000166:cytology / Q000187:drug effects
D018501:Antirheumatic Agents; D018932:Chemokine CCL2; D018946:Chemokine CCL5; D007375:Interleukin-1; D010666:Phenylpropionates; C078547:esonarimod