MinireviewCytochrome P450 expression in human keratinocytes: an aryl hydrocarbon receptor perspective
Section snippets
The skin: an important site of chemical exposure with self-renewing properties
As an important interface between an individual and his/her environment, the skin is a major site of direct exposure to many pharmaceutical and toxic agents. These exposures may occur occupationally through direct contact with adverse chemicals, environmentally through exposure to airborne pollutants, therapeutically through the administration of topical creams, or via a number of systemic exposures. While these exposures may result in a number of adverse outcomes such as contact dermatitis,
Expression of CYPs involved in xenobiotic/drug metabolism
Many of the CYPs that have been characterized to play major roles in xenobiotic/drug metabolism in the liver have also been identified in human skin (Table 1). Included in this group are the CYPs that are involved in the metabolism of many procarcinogens (i.e. CYP1A1, CYP1A2, CYP1B1, CYP2A6, CYP2B6 and CYP3A4) and the majority of pharmaceutical drugs (i.e. CYP3A4/5 and CYP2D6) [12], [13], [14], [15]. Since in vitro culturing of keratinocytes, like many cell types, dramatically alters the
Induction of CYP expression in human keratinocytes
As shown in Table 1, the expression levels of distinct subsets of CYPs have been reported to be regulated by a number of nuclear receptors [33], [34], [35], [36], [37], [38]. However, it should be noted that the evidence presented here has been obtained from studies that were performed primarily in hepatocytes. Evidence that many of the ‘classic’ inducers of the CYPs are functional in human keratinocytes has been demonstrated [13]. This includes the induction of CYP2B by phenobarbital (CAR, [35]
Consequences of alterations in CYP expression
The fact that the skin expresses a variety of CYPs involved in diverse signaling pathways has pharmacological and toxicological consequences, many of which are undiscovered. The number of pharmaceutical products that are administered topically has increased dramatically in recent years. In addition to the standard creams and ointments that act as anti-inflammatories (i.e. dexamethasone, betamethasone and hydrocortisone), antibiotics (i.e. erythromycin), and antifungals (i.e. ketaconazole), a
Summary
This review has highlighted a number important aspects with respect to the CYPs expressed in human keratinocytes. A striking observation is the need for future research to close the gaps in our understanding of how CYPs and their regulation contribute to the etiology of skin diseases and their therapies.
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