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• W2061192406 abstract "There is evidence from human and animal research that 5-hydroxytryptamine (5-HT) 3 receptor antagonists, particularly tropisetron, exert analgesic and anti-inflammatory activity. We have demonstrated that tropisetron inhibited lipopolysaccharide (LPS)-stimulated tumor necrosis factor (TNF)alpha and interleukin-(IL-)1beta release in primary human monocytes. The underlying mechanisms of these effects have not been investigated in detail so far.The molecular mechanisms of the anti-inflammatory effects of tropisetron were investigated in human primary monocytes in vitro by studying IL-1beta and TNFalpha mRNA levels by PCR and reporter gene assay and by elucidating the phosphorylation of p38 mitogen activated kinase (MAPK) by Western blot.The steady state levels of IL-1beta and TNFalpha mRNA in LPS-activated human peripheral monocytes and the transcriptional activity of the TNFalpha promoter were not inhibited by tropisetron, suggesting that the inhibitory activity of this 5-HT₃ receptor antagonist takes place at the post-transcriptional level. Additionally, we found that tropisetron prevents the phosphorylation and thus activation of the p38 MAPK, which is involved in post-transcriptional regulation of various cytokines.Our data indicate that the anti-inflammatory effects of the 5-HT₃ receptor antagonist tropisetron, as shown in vivo, are possibly mediated by a selective inhibition of pro-inflammatory cytokines at the post-transcriptional level. 5-HT₃ receptor antagonists are therefore a new and promising therapeutic option. New and more selective--in respect to the 5-HT₃ subtypes--5-HT₃R antagonists might be a future perspective in the pharmacological treatment of inflammatory diseases." @default.
• W2061192406 created "2016-06-24" @default.
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• W2061192406 date "2012-08-01" @default.
• W2061192406 modified "2023-10-16" @default.
• W2061192406 title "The anti-inflammatory effects of the 5-HT3 receptor antagonist tropisetron are mediated by the inhibition of p38 MAPK activation in primary human monocytes" @default.
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• W2061192406 doi "https://doi.org/10.1016/j.intimp.2012.05.013" @default.
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