BACKGROUND: Seborrhoeic keratosis (SK) is a benign epidermal tumour with increased pigmentation. We have recently demonstrated that increased secretion of endothelin (ET)-1, a strong keratinocyte-derived mitogen and melanogen for human melanocytes, is intrinsically involved in the hyperpigmentation mechanism of SK. OBJECTIVES: To examine whether the increased ET secretion results from cytokines that induce ET production and/or from differences in the processing of ET that lead to its final active, secreted form. METHODS: We used immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR) to determine whether ET-inducing enzymes and/or cytokines are also highly expressed in SK. RESULTS: RT-PCR of mRNAs encoding interleukin (IL)-1alpha, tumour necrosis factor (TNF)-alpha and endothelin-converting enzyme (ECE)-1alpha demonstrated that there is an increased expression of TNF-alpha and ECE-1alpha mRNAs in SK, whereas the IL-1alpha transcript is rather downregulated in SK compared with that in perilesional normal epidermis. In parallel, immunohistochemical analysis of SK revealed marked immunostaining for TNF-alpha in basaloid cells at lower levels of the epidermis and in basal cells, and for ECE-1alpha in most basaloid and basal cells in comparison with their weak staining throughout the epidermis in perilesional normal controls. In contrast, immunostaining for IL-1alpha was almost negative in SK relative to distinctive staining throughout the epidermis in the perilesional normal controls. CONCLUSIONS: These findings suggest that the increased secretion of ET-1 leading to enhanced pigmentation in SK results from the co-ordinated increased expression of TNF-alpha and ECE-1alpha.
BACKGROUND:Seborrhoeic keratosis (SK) is a benign epidermal tumour with increased pigmentation. We have recently demonstrated that increased secretion of endothelin (ET)-1, a strong keratinocyte-derived mitogen and melanogen for human melanocytes, is intrinsically involved in the hyperpigmentation mechanism of SK. OBJECTIVES: To examine whether the increased ET secretion results from cytokines that induce ET production and/or from differences in the processing of ET that lead to its final active, secreted form. METHODS: We used immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR) to determine whether ET-inducing enzymes and/or cytokines are also highly expressed in SK. RESULTS: RT-PCR of mRNAs encoding interleukin (IL)-1alpha, tumour necrosis factor (TNF)-alpha and endothelin-converting enzyme (ECE)-1alpha demonstrated that there is an increased expression of TNF-alpha and ECE-1alpha mRNAs in SK, whereas the IL-1alpha transcript is rather downregulated in SK compared with that in perilesional normal epidermis. In parallel, immunohistochemical analysis of SK revealed marked immunostaining for TNF-alpha in basaloid cells at lower levels of the epidermis and in basal cells, and for ECE-1alpha in most basaloid and basal cells in comparison with their weak staining throughout the epidermis in perilesional normal controls. In contrast, immunostaining for IL-1alpha was almost negative in SK relative to distinctive staining throughout the epidermis in the perilesional normal controls. CONCLUSIONS: These findings suggest that the increased secretion of ET-1 leading to enhanced pigmentation in SK results from the co-ordinated increased expression of TNF-alpha and ECE-1alpha.