Abstract
The aim of this study was to evaluate the anti-inflammatory effect of 4-hydroxy-2-methyl-N-[5-methyl-2-thiazolyl]-2H-1, 2-benzothiazine-3-carboxamide-1,1-dioxide (meloxicam) using cultured rheumatoid synovial fibroblast-like cells (synoviocytes). Synoviocytes were treated with meloxicam in the presence or absence of interleukin-1beta. Meloxicam had no effect on both cyclooxygenase-1 and -2 expression as determined by Western blot analysis, immunohistochemical staining, and reverse transcription polymerase chain reaction (RT-PCR). Even the lower doses of meloxicam inhibited cyclooxygenase-2 activity, but only the higher doses of meloxicam inhibited cyclooxygenase-1 activity as determined by prostaglandin E(2) synthesis assay. So meloxicam had a preferential inhibitory effect of cyclooxygenase-2 relative to cyclooxygenase-1 on cultured rheumatoid synoviocytes without affecting cyclooxygenase expression. On the other hand, indomethacin had no selectivity and dexamethasone inhibited the expression of cyclooxygenase-2. Our data indicate that clinical efficacy and safety of meloxicam for rheumatoid arthritis may result from its preferential inhibition of cyclooxygenase-2 activity relative to cyclooxygenase-1 on rheumatoid synoviocytes.
MeSH terms
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Anti-Inflammatory Agents / pharmacology
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Anti-Inflammatory Agents, Non-Steroidal / pharmacology
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Arthritis, Rheumatoid / drug therapy*
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Arthritis, Rheumatoid / enzymology
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Arthritis, Rheumatoid / pathology
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Blotting, Western
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Cells, Cultured
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Cyclooxygenase 1
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Cyclooxygenase 2
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Cyclooxygenase 2 Inhibitors
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Cyclooxygenase Inhibitors / pharmacology*
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Dexamethasone / pharmacology
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Dinoprostone / metabolism
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Dose-Response Relationship, Drug
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Gene Expression Regulation, Enzymologic / drug effects
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Humans
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Immunohistochemistry
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Indomethacin / pharmacology
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Isoenzymes / drug effects*
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Isoenzymes / genetics
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Isoenzymes / metabolism
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Meloxicam
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Membrane Proteins
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Prostaglandin-Endoperoxide Synthases / drug effects*
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Prostaglandin-Endoperoxide Synthases / genetics
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Prostaglandin-Endoperoxide Synthases / metabolism
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RNA, Messenger / drug effects
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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Synovial Membrane / cytology
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Synovial Membrane / drug effects*
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Synovial Membrane / enzymology
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Thiazines / pharmacology*
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Thiazoles / pharmacology*
Substances
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Anti-Inflammatory Agents
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Anti-Inflammatory Agents, Non-Steroidal
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Cyclooxygenase 2 Inhibitors
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Cyclooxygenase Inhibitors
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Isoenzymes
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Membrane Proteins
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RNA, Messenger
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Thiazines
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Thiazoles
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Dexamethasone
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Cyclooxygenase 1
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Cyclooxygenase 2
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PTGS1 protein, human
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PTGS2 protein, human
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Prostaglandin-Endoperoxide Synthases
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Dinoprostone
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Meloxicam
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Indomethacin