Retinoids induce apoptosis in cultured keratinocytes.
BACKGROUND
Apoptosis is a genetically controlled process linked to growth and differentiation, involving specific molecular and cellular events activated as a result of a variety of internal and external stimuli.


OBJECTIVE
To examine the ability of physiological and synthetic retinoids to induce apoptosis in the BALB/MK mouse keratinocyte cell line.


METHODS
Cell viability was assessed by flow cytometry, various staining techniques and the TUNEL method.


RESULTS
When keratinocytes were simultaneously exposed to retinoids and stimulated to differentiate at a high (1.5 mmol L(-1))extracellular Ca(2+) concentration over 48 h, apoptosis was induced. Of the retinoids tested, 3,4-didehydroretinoic acid and 3-methyl-tetrahydro-tetramethyl-naphthylenyl-propenyl benzoic acid were more potent than the others. In this system, the apoptosis induced by retinoids could not be correlated to the expression of tissue transglutaminase or epidermal transglutaminase. Furthermore, expression of antiapoptotic bcl-2 or proapoptotic Bax did not change significantly under the experimental conditions used, indicating that the regulation of apoptosis is complex and may be influenced by different factors.


CONCLUSIONS
The results suggest that retinoids activating either retinoic acid receptors or retinoid X receptors can induce apoptosis in cultured keratinocytes. Moreover, the well-established inhibitory effect of retinoids on keratinocyte differentiation implies that the apoptotic programme represents a distinct biological process.
Islam
T C
TC
Department of Biosciences and Center for Biotechnology, Huddinge Hospital, Division of Clinical Immunology, Karolinska Institutet, SE-141 86 Huddinge, Sweden.
Skarin
T
T
Sumitran
S
S
Toftgård
R
R
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D005786:Gene Expression Regulation / Q000187:drug effects; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012176:Retinoids / Q000494:pharmacology*; D018626:Retroelements / Q000235:genetics; D011503:Transglutaminases / Q000378:metabolism; D051028:bcl-2-Associated X Protein
C494827:Bax protein, mouse; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012176:Retinoids; D018626:Retroelements; D051028:bcl-2-Associated X Protein; D011503:Transglutaminases