Retinoids induce apoptosis in cultured keratinocytes

Background Apoptosis is a genetically controlled process linked to growth a nd differentiation, involving specific molecular and cellular events activa ted as a result of a variety of internal and external stimuli. Objectives 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 tec hniques and the TUNEL method. Results When keratinocytes were simultaneously exposed to retinoids and sti mulated to differentiate at a high (1.5 mmol L-1) extracellular Ca2+ concen tration over 48 h, apoptosis was induced. Of the retinoids tested, 3,4-dide hydroretinoic acid and 3-methyl-tetrahydro-tetramethyl-naphthylenyl-propeny l benzoic acid were more potent than the others. In this system, the apopto sis induced by retinoids could not be correlated to the expression of tissu e transglutaminase or epidermal transglutaminase. Furthermore, expression o f antiapoptotic bcl-2 or proapoptotic Bax did not change significantly unde r the experimental conditions used, indicating that the regulation of apopt osis is complex and may be influenced by different factors. Conclusions The results suggest that retinoids activating either retinoic a cid receptors or retinoid X receptors can induce apoptosis in cultured kera tinocytes. Moreover, the well-established inhibitory effect of retinoids on keratinocyte differentiation implies that the apoptotic programme represen ts a distinct biological process.