Effects of tenidap on intracellular signal transduction and the induction of proinflammatory cytokines: a review.
Tenidap is a novel, once-daily antirheumatic drug which has shown promising results against rheumatoid arthritis in extensive clinical trials. It combines NSAID-like cyclooxygenase inhibition with suppression of the acute phase response. In macrophages, tenidap inhibits the lipopolysaccharide-induced synthesis of interleukins-1 and -6, but it tends to potentiate the lipopolysaccharide-induced synthesis of tumor necrosis factor alpha, due to its cyclooxygenase inhibition. In macrophages, tenidap is a potent inhibitor of zymosan-induced responses, not only the induction of proinflammatory cytokines, but also arachidonate mobilization, protein phosphorylation, and inositol phosphate formation, possibly through interference with the receptor-mediated upregulation of phospholipase C. Tenidap also acts as an intracellular acidifier in many cell types, which may explain at least some of its other effects. Recent studies have indicated that, in addition to modulation of prostanoid and cytokine formation, tenidap has many other effects beneficial in rheumatic disease. It has been shown to inhibit bone resorption, neutrophil adhesion and degranulation, the interleukin-1-induced suppression of glycosaminoglycan synthesis, as well as the production of active metalloproteinases from chondrocytes.
Department of Cell and Molecular Biology, Lund University, Sweden.
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Bondeson
D000210:Acute-Phase Reaction; D000818:Animals; D018501:Antirheumatic Agents / Q000494:pharmacology*; D016718:Arachidonic Acid / Q000378:metabolism; D001842:Bone and Bones / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002356:Cartilage / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis*; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D007295:Inositol Phosphates / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology; D000078183:Oxindoles; D015398:Signal Transduction / Q000187:drug effects*
D018501:Antirheumatic Agents; D016207:Cytokines; D007211:Indoles; D007295:Inositol Phosphates; D000078183:Oxindoles; D016718:Arachidonic Acid; C062866:tenidap; D002118:Calcium