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Methotrexate induces apoptotic cell death in human keratinocytes
M Heenen1, M Laporte, J C Noel
1Department of Dermatology, Hôpital Erasme, Université Libre de Bruxelles, Belgium.
Archives of Dermatological Research
|July 29, 1998
Summary
Low doses of methotrexate induce apoptosis, a programmed cell death, in keratinocytes. This mechanism may explain how methotrexate treatment reduces skin thickening in psoriasis.
Area of Science:
- Dermatology
- Cell Biology
- Pharmacology
Background:
- The mechanism of low-dose methotrexate in psoriasis treatment is unclear.
- Psoriasis involves epidermal hyperplasia.
- Apoptosis is programmed cell death crucial for tissue homeostasis.
Purpose of the Study:
- To investigate if low-dose methotrexate induces apoptosis in keratinocytes.
- To explore the role of p53 in methotrexate-induced keratinocyte apoptosis.
Main Methods:
- Organotypical keratinocyte culture model on deepidermized dermis.
- Treatment with low-dose methotrexate (10(-7) M).
- Histology, TUNEL assay, p53 immunohistochemistry, and electron microscopy.
Main Results:
- Methotrexate induced morphological features of apoptosis in 1% of keratinocytes.
- Overexpression of p53 was observed in the basal layer of treated cultures.
- DNA fragmentation, a marker of apoptosis, was detected.
Conclusions:
- Low-dose methotrexate effectively induces apoptosis in keratinocytes.
- This apoptotic effect could underlie the reduction in epidermal hyperplasia in psoriasis patients.
- The study highlights apoptosis as a key mechanism in methotrexate therapy for psoriasis.