title: The mechanism of hyperpigmentation in seborrhoeic keratosis involves the high expression of endothelin-converting enzyme-1alpha and TNF-alpha, which stimulate secretion of endothelin 1.
abstract: 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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Department of Dermatology, Tokyo Women's Medical University, Japan.
authors.forename: L
authors.initials: L
authors.lastname: Manaka
authors.forename: S
authors.initials: S
authors.lastname: Kadono
authors.forename: M
authors.initials: M
authors.lastname: Kawashima
authors.forename: T
authors.initials: T
authors.lastname: Kobayashi
authors.forename: G
authors.initials: G
authors.lastname: Imokawa
mesh_terms: D018929:Cell Culture Techniques; D019332:Endothelin-1 / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D017495:Hyperpigmentation / Q000209:etiology* / Q000378:metabolism; D007124:Immunoenzyme Techniques; D015603:Keratinocytes / Q000378:metabolism; D017492:Keratosis, Seborrheic / Q000150:complications* / Q000378:metabolism; D008666:Metalloendopeptidases / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*
chemical_list: D019332:Endothelin-1; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C492359:ECEL1 protein, human; D008666:Metalloendopeptidases