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| Item type: | Article | ||||
|---|---|---|---|---|---|
| Journal or Publication Title: | Biochemical Pharmacology | ||||
| Publisher: | Elsevier | ||||
| Volume: | 66 | ||||
| Number of Issue or Book Chapter: | 11 | ||||
| Page Range: | pp. 2141-2153 | ||||
| Date: | 2003 | ||||
| Additional Information (public): | CAN 140:174629 1-6 Pharmacology 302788-42-7 Role: BSU (Biological study, unclassified), BIOL (Biological study) (gene for; influence of helenanolide-type sesquiterpene lactones on gene transcription profiles in JURKAT and human mononuclear cells and mechanism of their anti-inflammatory and cytotoxic effects); 6754-13-8 (Helenalin); 36505-53-0 (Dihydrohelenalin acetate); 78853-98-2 (Chamissonolide) Role: DMA (Drug mechanism of action), PAC (Pharmacological activity), BIOL (Biological study) (influence of helenanolide-type sesquiterpene lactones on gene transcription profiles in JURKAT and human mononuclear cells and mechanism of their anti-inflammatory and cytotoxic effects); 501433-35-8 (INOS) Role: BSU (Biological study, unclassified), BIOL (Biological study) (mRNA; influence of helenanolide-type sesquiterpene lactones on gene transcription profiles in JURKAT and human mononuclear cells and mechanism of their anti-inflammatory and cytotoxic effects) | ||||
| Institutions: | Chemistry and Pharmacy > Institute of Pharmacy > Pharmaceutical Biology (Prof. Heilmann) | ||||
| Identification Number: |
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| Keywords: | Gene Role: BSU (Biological study, unclassified), BIOL (Biological study) (Bcl-2 influence of helenanolide-type sesquiterpene lactones on gene transcription profiles in JURKAT and human mononuclear cells and mechanism of their anti-inflammatory and cytotoxic effects) Cyclins Role: BSU (Biological study, unclassified), BIOL (Biological study) (D1, gene for influence of helenanolide-type sesquiterpene lactones on gene transcription profiles in JURKAT and human mononuclear cells and mechanism of their anti-inflammatory and cytotoxic effects) Transcription factors Role: BSU (Biological study, unclassified), BIOL (Biological study) (IkB-alpha (NF-kB inhibitor alpha ), gene for influence of helenanolide-type sesquiterpene lactones on gene transcription profiles in JURKAT and human mononuclear cells and mechanism of their anti-inflammatory and cytotoxic effects) Animal cell line (JURKAT influence of helenanolide-type sesquiterpene lactones on gene transcription profiles in JURKAT and human mononuclear cells and mechanism of their anti-inflammatory and cytotoxic effects) Transcription factors Role: BSU (Biological study, unclassified), BIOL (Biological study) (NF-kB (nuclear factor of k light chain gene enhancer in B-cells) influence of helenanolide-type sesquiterpene lactones on gene transcription profiles in JURKAT and human mononuclear cells and mechanism of their anti-inflammatory and cytotoxic effects) Transcription factors Role: BSU (Biological study, unclassified), BIOL (Biological study) (NFAT2 (nuclear factor of activated T-cell, 2), gene for influence of helenanolide-type sesquiterpene lactones on gene transcription profiles in JURKAT and human mononuclear cells and mechanism of their anti-inflammatory and cytotoxic effects) Immunity (cell-mediated influence of helenanolide-type sesquiterpene lactones on gene transcription profiles in JURKAT and human mononuclear cells and mechanism of their anti-inflammatory and cytotoxic effects) Gene Role: BSU (Biological study, unclassified), BIOL (Biological study) (house-keeping influence of helenanolide-type sesquiterpene lactones on gene transcription profiles in JURKAT and human mononuclear cells and mechanism of their anti-inflammatory and cytotoxic effects) Anti-inflammatory agents Apoptosis Cytotoxic agents Human Mononuclear cell Transcription (influence of helenanolide-type sesquiterpene lactones on gene transcription profiles in JURKAT and human mononuclear cells and mechanism of their anti-inflammatory and cytotoxic effects) Transcriptome mRNA Role: BSU (Biological study, unclassified), BIOL (Biological study) (influence of helenanolide-type sesquiterpene lactones on gene transcription profiles in JURKAT and human mononuclear cells and mechanism of their anti-inflammatory and cytotoxic e Sesquiterpenes Role: DMA (Drug mechanism of action), PAC (Pharmacological activity), BIOL (Biological study) (lactones influence of helenanolide-type sesquiterpene lactones on gene transcription profiles in JURKAT and human mononuclear cells and mechanism of their anti-inflammatory and cytotoxic effects) Cytokines Role: BSU (Biological study, unclassified), BIOL (Biological study) (mitogen-induced influence of helenanolide-type sesquiterpene lactones on gene transcription profiles in JURKAT and human mononuclear cells and mechanism of their anti-inflammatory and cytotoxic effects) Proteins Role: BSU (Biological study, unclassified), BIOL (Biological study) (p65, gene for influence of helenanolide-type sesquiterpene lactones on gene transcription profiles in JURKAT and human mononuclear cells and mechanism of their anti-inflammatory and cytotoxic effects) Actins Role: BSU (Biological study, unclassified), BIOL (Biological study) (beta -, gene for influence of helenanolide-type sesquiterpene lactones on gene transcription profiles in JURKAT and human mononuclear cells and mechanism of their anti-inflammatory and cytotoxic effects) helenanolide sesquiterpene lactone apoptosis antiinflammatory cytotoxic NFkappaB | ||||
| Dewey Decimal Classification: | 500 Science > 570 Life sciences 500 Science > 540 Chemistry & allied sciences | ||||
| Status: | Published | ||||
| Refereed: | Yes, this version has been refereed | ||||
| Created at the University of Regensburg: | No | ||||
| Item ID: | 17212 |
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-kB (p65), which is a pivotal regulator of the cellular immune response. Since NF-kB is involved in the transcriptional control of several pro-inflammatory and regulatory ...
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-kB (p65), which is a pivotal regulator of the cellular immune response. Since NF-kB is involved in the transcriptional control of several pro-inflammatory and regulatory genes, we investigated the effects of one bifunctional NF-kB (p65) inhibiting and two monofunctional NF-kB (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 11alpha ,13-dihydrohelenalin acetate (DHAc) and chamissonolide significantly reduced mitogen-induced cytokine and iNOS mRNA levels in PBMCs and Jurkat T cells at low micromolar concns. DHAc also showed significant effects on the gene expression of the house-keeping genes GAP-DH and beta -actin, as well as on NF-ATc, p65, I-kBalpha , bcl-2, and cyclin D1. The bifunctional NF-kB 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-kB (p65) DNA-binding at concns. effective on the transcriptome. Thus, it can be concluded that the biol. effects of SLs are not only due to NF-kB inhibition, but must be coupled to other mechanisms.
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