The differentiation-related upregulation of aryl hydrocarbon receptor transcript levels is suppressed by retinoic acid.

The environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) binds to a specific intracellular receptor protein -the Ah-receptor- which acts as a transcription factor. Herein we report on the relative levels of Ah-receptor-mRNA and TCDD-induced cytochrome P450 1A1 (Cyp1A1)-mRNA and their modulation by retinoic acid in the human keratinocyte cell line HaCaT. Ah-receptor-mRNA was already present in proliferating keratinocytes and increased 8-fold in the course of differentiation. Addition of 10 nM TCDD did not alter the level of Ah-receptor transcripts. In contrast, addition of 1 microM RA maintained the amount of Ah-receptor-mRNA at the basal level as observed only in proliferating keratinocytes. The transcription of Cyp1A1 was dependent on TCDD-treatment and increased fivefold in more differentiated cells as compared to proliferating cells. Simultaneous addition of retinoic acid revealed an only twofold increase. These results indicate that the expression of the AhR is dependent on the state of differentiation of keratinocytes and seems to be affected by retinoic acid.