Cytochrome P450, CYP26AI, is expressed at low levels in human epidermal keratinocytes and is not retinoic acid-inducible

Retinoids, and their synthetic analogues, are well-established regulators o f the squamous differentiation programme both in vivo and in vitro. Despite this, very few studies have focused on the mechanism by which retinoid act ion is terminated, e.g. metabolism, Recently, a new cytochrome P450 family member (CYP26AI) was cloned. CUP26AI was reported to have substrate specifi city for retinoids and to be retinoid-inducible. In this study, we have exa mined the expression and retinoic acid (RA) inducibility of CYP26AI in huma n epidermis and cultured keratinocytes. We found very low levels of CYP26AI mRNA expression in both epidermis and keratinocytes. Furthermore, we found no evidence for RA inducibility of CYP26 mRNA expression, This lack of RA inducibility was not due to inactivity of the retinoids, as we show that tr ansglutaminase was still repressed by RA in the same cultures. Despite the lo iv levels of CYP26AI expression in the keratinocytes, the keratinocytes were still capable of significant RA metabolism, In conclusion, our study r eports, for the first time, that CYP26AI is unlikely to contribute to RA me tabolism in keratinocytes. These studies also indicate that. as pet unknown isoforms of cytochrome P450 may be involved in RA metabolism in keratinocy tes.