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Induction of apoptotic cell death by IFNbeta on HPV-16 transformed human keratinocytes
F De Marco1, V Manni, N Guaricci
1Laboratory of Virology, Regina Elena Institute for Cancer Research, Rome, Italy. demarco@crs.ifo.it
Abstract:
Apoptosis, or 'programmed cell death' is a process of general biological relevance with implications in several physiological and pathological conditions of the skin. However, little is known about its induction in keratinocytes by regulator agents. In this work we demonstrate that IFNbeta, but not IFNalpha, selectively induces programmed cell death in HPK-Ia cells, a line derived from human keratinocytes transformed with HPV-16 DNA. This IFNbeta-triggered apoptosis is strictly dependent on a serum-induced partially differentiated phenotype; it occurs through the activation of a check point in the early 'S' phase, where the cells are arrested and eventually driven to apoptosis. These data indicate that apoptosis may be induced in keratinocytes by a regulator agent combined with a differentiating stimulus.
Insights
Interferon beta (IFNbeta) selectively triggers programmed cell death in human keratinocytes. This apoptosis requires a partially differentiated state and occurs during the S phase of the cell cycle.
Area of Science:
- Cell Biology
- Immunology
- Dermatology
Background:
- Apoptosis is crucial in skin physiology and pathology.
- Keratinocyte apoptosis induction by regulatory agents is poorly understood.
Purpose of the Study:
- To investigate the induction of apoptosis in human keratinocytes by regulatory agents.
- To determine the specific role of Interferon alpha (IFNalpha) and Interferon beta (IFNbeta) in keratinocyte apoptosis.
Main Methods:
- Utilized HPK-Ia cells, a human keratinocyte line transformed with HPV-16 DNA.
- Administered IFNalpha and IFNbeta to cell cultures.
- Assessed apoptosis induction and cell cycle progression.
- Investigated the role of serum-induced differentiation.
Main Results:
- IFNbeta, but not IFNalpha, selectively induced apoptosis in HPK-Ia cells.
- IFNbeta-triggered apoptosis was dependent on a serum-induced partially differentiated phenotype.
- Apoptosis occurred via cell cycle arrest at the early S phase.
Conclusions:
- IFNbeta can induce programmed cell death in keratinocytes.
- A combination of a regulatory agent (IFNbeta) and a differentiating stimulus is necessary for keratinocyte apoptosis.
- This finding has implications for understanding skin conditions involving keratinocyte apoptosis.