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Inhibition of TNF-induced apoptosis by NF-kappa B
D J Van Antwerp1, S J Martin, I M Verma
1Laboratory of Genetics, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Abstract:
Tumour necrosis factor (TNF) is an inflammatory cytokine possessing a unique property: it can induce cells to undergo apoptosis. The sensitivity of different cell types to TNF-induced apoptosis can vary dramatically, but most cells become very sensitive upon simultaneous treatment with inhibitors of protein synthesis. It has been suggested therefore that a gene, or set of genes, is induced upon TNF receptor activation that downregulates the apoptosis signal. Recent results have shown that NF-kappa B, a transcription factor activated upon TNF signalling, is at least partly responsible for this effect. These findings have broadened the role of NF-kappa B from that of a regulator of immune and inflammatory responses to include an involvement in the regulation of apoptosis.
Insights
Tumour necrosis factor (TNF) can trigger cell death (apoptosis). Protein synthesis inhibitors enhance TNF-induced apoptosis, revealing a regulatory role for NF-kappa B in controlling this cell death pathway.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Tumour necrosis factor (TNF) is a key inflammatory cytokine.
- TNF induces apoptosis (programmed cell death) in various cell types.
- Cellular sensitivity to TNF-induced apoptosis is highly variable.
Purpose of the Study:
- To investigate the mechanisms regulating TNF-induced apoptosis.
- To identify genes involved in downregulating the apoptosis signal upon TNF receptor activation.
- To elucidate the role of NF-kappa B in apoptosis regulation.
Main Methods:
- Utilized TNF treatment in cell cultures.
- Employed protein synthesis inhibitors to modulate apoptosis sensitivity.
- Investigated the activation of NF-kappa B signaling pathway.
Main Results:
- Most cells become highly sensitive to TNF-induced apoptosis when protein synthesis is inhibited.
- TNF receptor activation induces genes that downregulate apoptosis.
- NF-kappa B, activated by TNF signaling, plays a significant role in this downregulation.
Conclusions:
- NF-kappa B is a crucial regulator of apoptosis.
- The role of NF-kappa B extends beyond immune and inflammatory responses to include apoptosis control.
- Understanding TNF and NF-kappa B interactions is vital for cancer and autoimmune disease research.