The mechanism of epidermal hyperpigmentation in café-au-lait macules of neurofibromatosis type 1 (von Recklinghausen's disease) may be associated with dermal fibroblast-derived stem cell factor and hepatocyte growth factor.
BACKGROUND
The mechanism of the accentuated melanization in café-au-lait macules (CALMs) in patients with neurofibromatosis type 1 (NF1; von Recklinghausen's disease) has not been elucidated.


OBJECTIVE
To clarify the mechanism involved in the hyperpigmentation of CALMs in NF1.


METHODS
Using enzyme-linked immunosorbent assay (ELISA) and reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of cultured cells, we measured the levels of cytokines produced and secreted by keratinocytes and fibroblasts derived from CALMs (group RC: Recklinghausen CALM) skin, compared with cells derived from the skin of normal individuals (group NN: Normal skin of Normal individuals) and cells derived from non-CALM skin of NF1 patients (group RN: Recklinghausen Non-CALM).


RESULTS
ELISA revealed that the secretion of hepatocyte growth factor (HGF) and stem cell factor (SCF) by cultured fibroblasts was significantly elevated in group RC compared with groups RN and NN. In parallel, semiquantitative real-time RT-PCR of HGF and SCF mRNAs demonstrated increased expression of both types of transcripts by cultured fibroblasts in group RC compared with group NN. In contrast, the secretion of endothelin-1 and granulocyte/macrophage colony-stimulating factor by cultured keratinocytes occurred at a similar level among all three groups, RC, RN and NN.


CONCLUSIONS
These findings suggest that increased secretion of HGF and SCF by dermal fibroblasts may be associated with the accentuated epidermal melanization observed in CALMs in the skin of NF1 patients.
Okazaki
M
M
Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, University of Tokyo 7-3-1, Hongo, Tokyo 3-86SS, Japan.
Yoshimura
K
K
Suzuki
Y
Y
Uchida
G
G
Kitano
Y
Y
Harii
K
K
Imokawa
G
G
D000328:Adult; D019080:Cafe-au-Lait Spots / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D002675:Child, Preschool; D017077:Culture Media, Conditioned; D016207:Cytokines / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D017228:Hepatocyte Growth Factor / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009456:Neurofibromatosis 1 / Q000378:metabolism* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019089:Stem Cell Factor / Q000235:genetics / Q000378:metabolism*
D017077:Culture Media, Conditioned; D016207:Cytokines; D019089:Stem Cell Factor; D017228:Hepatocyte Growth Factor