Differential effects of tenidap on the zymosan- and lipopolysaccharide-induced expression of mRNA for proinflammatory cytokines in macrophages.
Tenidap is a novel antirheumatic drug that combines cyclooxygenase inhibition with cytokine modulating qualities. We demonstrate here that tenidap inhibits the zymosan-induced expression of both interleukin 1 and tumor necrosis factor alpha in macrophages, at the mRNA and protein levels. The concentration-dependence of the tenidap-induced inhibition of the expression of mRNA for these proinflammatory cytokines agrees with that of its inhibitory effects on zymosan-induced arachidonate mobilization and changes in phosphoprotein pattern. The effects of tenidap on the lipopolysaccharide-induced expression of these cytokines are more complex. Tenidap inhibits the induction of interleukin 1 by lipopolysaccharide or bacteria, but less potently than the interleukin 1-response induced by zymosan. In contrast, the drug markedly potentiates the lipopolysaccharide-induced expression of tumor necrosis factor alpha at both the mRNA and protein levels. The latter effect is demonstrated to be due to cyclooxygenase inhibition and is reversed by prostaglandin E2.
Bondeson
J
J
Department of Cell and Molecular Biology, Lund University, Sweden.
Sundler
R
R
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001483:Base Sequence; D000001:Calcimycin / Q000494:pharmacology; D004789:Enzyme Activation; D005260:Female; D007211:Indoles / Q000494:pharmacology*; D007375:Interleukin-1 / Q000235:genetics*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D000078183:Oxindoles; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics*; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D015054:Zymosan / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007211:Indoles; D007375:Interleukin-1; D008070:Lipopolysaccharides; D015345:Oligonucleotide Probes; D000078183:Oxindoles; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D000001:Calcimycin; D015054:Zymosan; C062866:tenidap