The antiinflammatory sesquiterpene lactone parthenolide inhibits NF-κB by targeting the IκB kinase complex
The transcription factor NF-κB is a key regulator of the cellular inflammatory and immune response. Therefore, components of the NF-κB-activating signaling pathways are frequent targets for antiinflammatory agents. This study shows that the sesquiterpene lactone parthenolide inhibits a common step i...
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| Main Authors: | , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
November 15, 1999
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| In: |
The journal of immunology
Year: 1999, Volume: 163, Issue: 10, Pages: 5617-5623 |
| ISSN: | 1550-6606 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://www.jimmunol.org/content/163/10/5617
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| Author Notes: | Steffen P. Hehner, Thomas G. Hofmann, Wulf Dröge, and M. Lienhard Schmitz |
| Summary: | The transcription factor NF-κB is a key regulator of the cellular inflammatory and immune response. Therefore, components of the NF-κB-activating signaling pathways are frequent targets for antiinflammatory agents. This study shows that the sesquiterpene lactone parthenolide inhibits a common step in NF-κB activation by preventing the TNF-α-induced induction of IκB kinase (IKK) and IKKβ, without affecting the activation of p38 and c-Jun N-terminal kinase. Parthenolide impairs NF-κB-dependent transcription triggered by expression of TNFR-associated factor-2, mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEKK1), and NF-κB-inducing kinase. This compound also prevents activation of both IKKs and DNA binding of NF-κB induced by MEKK and NF-κB-inducing kinase. Parthenolide targets a component of the IκB kinase complex without directly inhibiting IKKα, IKKβ, or MEKK1. Therefore, this sesquiterpene lactone could serve as a lead compound for the development of antiinflammatory remedies and is suitable as a molecular tool, allowing the dissection of TNF-α-derived signaling pathways leading to the activation of NF-κB, c-Jun N-terminal kinase, and p38. |
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| Item Description: | Gesehen am 03.02.2021 |
| Physical Description: | Online Resource |
| ISSN: | 1550-6606 |