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Post-translational processing of tumor necrosis factor production
N Kitahara-Tanabe1, Y Tanabe, A Morikawa
1Biotechnology Research Center, Teikyo University, Kawasaki, Japan.
Chemical & Pharmaceutical Bulletin
|February 1, 1991
Summary
This study reveals that Bacillus Calmette-Guerin (BCG) priming leads to macrophage synthesis of precursor tumor necrosis factor (TNF) molecules. Lipopolysaccharide (LPS) triggering then facilitates the secretion of active, smaller TNF (p17) through post-translational processing.
Area of Science:
- Immunology
- Molecular Biology
- Cell Biology
Background:
- Tumor necrosis factor (TNF) is a key cytokine in immune responses.
- Understanding the precise mechanisms of TNF production is crucial for therapeutic development.
Purpose of the Study:
- To elucidate the molecular mechanisms underlying tumor necrosis factor (TNF) production in macrophages.
- To identify precursor and processed forms of TNF involved in its secretion.
Main Methods:
- Analysis of proteins synthesized by Bacillus Calmette-Guerin (BCG)-primed rabbit alveolar macrophages.
- In vitro culture with 35S-methionine and immunoprecipitation using anti-rabbit TNF monoclonal antibody.
- In vitro translation of messenger ribonucleic acid (mRNA) from primed macrophages.
Main Results:
- BCG-primed macrophages synthesized intracellular precursor proteins (p50 and p17) sharing TNF epitopes.
- Lipopolysaccharide (LPS) triggering induced the release of TNF activity and p17 into the medium.
- In vitro translation identified a primary TNF precursor of 28 kDa (p28).
Conclusions:
- TNF production involves post-translational processing of precursor molecules synthesized during BCG priming.
- The active, secreted form of TNF (p17) is released upon triggering, likely via processing of p28.
- This study clarifies the pathway from precursor synthesis to active TNF secretion.