Psoralen-ultraviolet A therapy alters epidermal Sema3A and NGF levels and modulates epidermal innervation in atopic dermatitis.
BACKGROUND
Epidermal nerve densities are increased in patients with atopic dermatitis (AD), suggesting that it is partly responsible for the intense itching in the skin. Epidermal hyperinnervation in AD patients is decreased by ultraviolet (UV) phototherapy, although the underlying mechanisms are poorly understood. Interestingly, abnormal expression of axonal guidance molecules, such as nerve growth factor (NGF) and semaphorin 3A (Sema3A), is found in the epidermis of AD patients. Therefore, UV phototherapy may alter levels of axonal guidance molecule expression in atopic skin.


OBJECTIVE
This study was performed to investigate whether epidermal Sema3A and NGF levels in AD are influenced by psoralen-UVA (PUVA) therapy.


METHODS
Skin biopsies obtained from chronic AD patients before and after PUVA therapy were used. Both Sema3A and NGF in the skin were examined at mRNA and protein levels by quantitative RT-PCR and immunohistochemistry, respectively. Nerve fibers in the skin were stained with anti-PGP9.5 antibody, and the number of epidermal nerve fibers was counted.


RESULTS
PUVA therapy decreased epidermal nerve densities in AD patients, concomitant with decreases in both visual analog scale (VAS) scores for pruritus and clinical severity scores. Increased fluorescence intensity of Sema3A and decreased fluorescence intensity of NGF were observed in the epidermis of PUVA-treated group. Moreover, Sema3A mRNA levels were upregulated in the PUVA-treated skins compared with untreated controls, while NGF mRNA levels in the skin were downregulated by the treatment.


CONCLUSIONS
PUVA therapy may reduce epidermal hyperinnervation of AD by normalization of abnormal Sema3A and NGF expression in the epidermis.
Tominaga
Mitsutoshi
M
Institute for Environmental and Gender Specific Medicine, Juntendo University Graduate School of Medicine, Urayasu, Chiba, Japan.
Tengara
Suhandy
S
Kamo
Atsuko
A
Ogawa
Hideoki
H
Takamori
Kenji
K
D000199:Actins / Q000378:metabolism; D000328:Adult; D002908:Chronic Disease; D003876:Dermatitis, Atopic / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004817:Epidermis / Q000187:drug effects* / Q000294:innervation* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D009412:Nerve Fibers / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D020932:Nerve Growth Factor / Q000096:biosynthesis; D011701:PUVA Therapy; D040121:Semaphorin-3A / Q000096:biosynthesis
D000199:Actins; D040121:Semaphorin-3A; D020932:Nerve Growth Factor