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Association of tumor necrosis factor-alpha gene expression and apoptotic cell death with regression of Shope
Y Hagari1, L R Budgeon, M D Pickel
1Department of Pathology, Milton S. Hershey Medical Center, Pennsylvania State University, Hershey, USA.
Abstract:
The objective of this study was to test the hypothesis that spontaneous regression of Shope papillomas involves tumor necrosis factor-alpha and apoptotic cell death of the papilloma cells. In situ hybridization using RNA probes of rabbit tumor necrosis factor-alpha revealed tumor necrosis factor-alpha mRNA in most of the numerous mononuclear cells infiltrating the upper dermis of regressing papillomas and at the dermoepidermal junction. Such cells in progressing papillomas were much fewer in number and were located in the deeper dermis. In situ terminal deoxynucleotidyl transferase assay demonstrated DNA strand breaks in many scattered epidermal keratinocytes of regressing papillomas but in only a few thin layers just beneath the horny layer in progressing papillomas. Electron microscopy demonstrated that regressing papillomas contained many apoptotic bodies and keratinocytes showing apoptotic changes such as chromatin condensation, degradation of condensed nuclei, surface protuberances, and a filamentous degeneration, as well as infiltrating lymphocytes and macrophages. We propose that tumor necrosis factor-alpha produced by infiltrating mononuclear cells probably plays a role in the papilloma regression.
Insights
Spontaneous Shope papilloma regression involves tumor necrosis factor-alpha (TNF-α) and apoptotic cell death. TNF-α mRNA and apoptotic keratinocytes were found in regressing tumors, suggesting TNF-α
Area of Science:
- Oncology
- Immunology
- Cell Biology
Background:
- Shope papillomas are benign skin tumors that can spontaneously regress.
- The mechanisms underlying papilloma regression are not fully understood.
- Tumor necrosis factor-alpha (TNF-α) and apoptosis are implicated in various regression processes.
Purpose of the Study:
- To investigate the role of TNF-α and apoptotic cell death in the spontaneous regression of Shope papillomas.
- To determine the localization and quantity of TNF-α mRNA and apoptotic cells in progressing versus regressing papillomas.
Main Methods:
- In situ hybridization to detect TNF-α mRNA.
- In situ terminal deoxynucleotidyl transferase assay to detect DNA strand breaks (apoptosis).
- Electron microscopy to examine cellular morphology and identify apoptotic bodies.
Main Results:
- TNF-α mRNA was abundant in mononuclear cells infiltrating regressing papillomas, particularly in the upper dermis and dermoepidermal junction.
- Fewer TNF-α-expressing cells were observed in deeper dermis of progressing papillomas.
- Significant DNA strand breaks and characteristic apoptotic changes (e.g., chromatin condensation, apoptotic bodies) were prevalent in epidermal keratinocytes of regressing papillomas.
- Electron microscopy confirmed widespread apoptosis and infiltration of lymphocytes and macrophages in regressing tumors.
Conclusions:
- The study supports the hypothesis that spontaneous Shope papilloma regression involves TNF-α and apoptotic cell death.
- TNF-α produced by infiltrating mononuclear cells likely plays a crucial role in mediating papilloma regression.
- Apoptotic keratinocyte death is a key feature of the regression process.