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- W2092164902 abstract "Sesquiterpene lactones (SLs) are known to have potent anti-inflammatory and cytotoxic properties. So far, the anti-inflammatory effects have mainly been attributed to their inhibition of DNA-binding of the transcription factor NF-κB (p65), which is a pivotal regulator of the cellular immune response. Since NF-κB is involved in the transcriptional control of several pro-inflammatory and regulatory genes, we investigated the effects of one bifunctional NF-κB (p65) inhibiting and two monofunctional NF-κB (p65) inactive helenanolide-type SLs on PMA and LPS-induced mRNA expression in CD4 + Jurkat T and human peripheral blood mononuclear cells (PBMCs) with reverse transcription real-time PCR (RT-rt-PCR). The monofunctional SLs 11α,13-dihydrohelenalin acetate (DHAc) and chamissonolide significantly reduced mitogen-induced cytokine and iNOS mRNA levels in PBMCs and Jurkat T cells at low micromolar concentrations. DHAc also showed significant effects on the gene expression of the house-keeping genes GAP-DH and β-actin, as well as on NF-ATc, p65, I-κBα, bcl-2, and cyclin D1. The bifunctional NF-κB inhibitor helenalin not only effectively inhibited pro-inflammatory gene expression, but also strongly down-regulated all investigated mRNA levels in a time-dependent manner. Flow cytometry and caspase-8 and -3 assays revealed that helenalin strongly and DHAc moderately induced apoptosis in Jurkat T cells, whereas chamissonolide caused cytoprotective effects. In PBMCs, DHAc and chamissonolide did not inhibit NF-κB (p65) DNA-binding at concentrations effective on the transcriptome. Thus, it can be concluded that the biological effects of SLs are not only due to NF-κB inhibition, but must be coupled to other mechanisms." @default.
- W2092164902 created "2016-06-24" @default.
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- W2092164902 date "2003-12-01" @default.
- W2092164902 modified "2023-09-29" @default.
- W2092164902 title "Influence of helenanolide-type sesquiterpene lactones on gene transcription profiles in Jurkat T cells and human peripheral blood cells: anti-inflammatory and cytotoxic effects" @default.
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- W2092164902 doi "https://doi.org/10.1016/j.bcp.2003.08.006" @default.
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