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Thalidomide induces apoptosis in human monocytes by using a cytochrome c-dependent pathway
Henning R Gockel1, Andreas Lügering, Jan Heidemann
1Department of Medicine B, University of Münster, Muenster, Germany.
Journal of Immunology (Baltimore, Md. : 1950)
|April 7, 2004
Summary
Thalidomide induces programmed cell death (apoptosis) in human monocytes, a key immune cell. This monocyte apoptosis, mediated by a mitochondrial pathway, may explain some of thalidomide's anti-inflammatory effects.
Area of Science:
- Immunology
- Pharmacology
- Cell Biology
Background:
- Thalidomide is an effective treatment for immunologic diseases like Crohn's disease and rheumatoid arthritis.
- Its anti-inflammatory effects are partly attributed to TNF-alpha inhibition, but the precise mechanism remains unclear.
- Induction of monocyte apoptosis is a common characteristic of anti-inflammatory agents.
Purpose of the Study:
- To investigate the role of thalidomide in inducing monocyte apoptosis.
- To elucidate the signaling pathways involved in thalidomide-mediated monocyte apoptosis.
Main Methods:
- Human peripheral blood monocytes were treated with thalidomide.
- Annexin V staining was used to detect apoptosis.
- Caspase activation, mitochondrial signaling, and specific receptor pathways (CD95, TNF-RI, TRAIL-R1) were analyzed.
Main Results:
- Thalidomide treatment induced time- and dose-dependent apoptosis in human monocytes.
- Monocyte apoptosis was dependent on caspase activation.
- The pathway involved AKT-1 kinase inhibition, mitochondrial cytochrome c release, and activation of caspase-9 and caspase-3, independent of CD95, TNF-RI, or TRAIL-R1.
Conclusions:
- Thalidomide induces monocyte apoptosis through a mitochondrial signaling pathway.
- This apoptosis may contribute to thalidomide's immunomodulatory and anti-inflammatory properties.