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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.

Abstract
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.
AuthorsT Inoue, M Yamashita, M Higaki
JournalRheumatology international (Rheumatol Int) Vol. 20 Issue 4 Pg. 149-53 (May 2001) ISSN: 0172-8172 [Print] Germany
PMID11411959 (Publication Type: Journal Article)
Chemical References
  • Antirheumatic Agents
  • Chemokine CCL2
  • Chemokine CCL5
  • Interleukin-1
  • Phenylpropionates
  • esonarimod
Topics
  • Aged
  • Animals
  • Antirheumatic Agents (pharmacology)
  • Arthritis, Rheumatoid (diagnosis, drug therapy)
  • Base Sequence
  • Cells, Cultured
  • Chemokine CCL2 (metabolism)
  • Chemokine CCL5 (biosynthesis)
  • Disease Models, Animal
  • Electrophoresis
  • Female
  • Humans
  • Interleukin-1 (pharmacology)
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Phenylpropionates (pharmacology)
  • Rats
  • Rats, Sprague-Dawley
  • Sensitivity and Specificity
  • Synovial Membrane (cytology, drug effects)

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