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.

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.

• Authors: L Manaka, S Kadono, M Kawashima, T Kobayashi, G Imokawa
• Journal: The British journal of dermatology (Br J Dermatol) Vol. 145 Issue 6 Pg. 895-903 (Dec 2001) ISSN: 0007-0963 [Print] England
• PMID: 11899142 (Publication Type: Journal Article)

Chemical References

• Endothelin-1
• RNA, Messenger
• Tumor Necrosis Factor-alpha
• ECEL1 protein, human
• Metalloendopeptidases

Topics

• Cell Culture Techniques
• Endothelin-1 (metabolism)
• Gene Expression
• Humans
• Hyperpigmentation (etiology, metabolism)
• Immunoenzyme Techniques
• Keratinocytes (metabolism)
• Keratosis, Seborrheic (complications, metabolism)
• Metalloendopeptidases (genetics, metabolism)
• RNA, Messenger (genetics)
• Reverse Transcriptase Polymerase Chain Reaction
• Tumor Necrosis Factor-alpha (genetics, metabolism)