Gene expression of enzymes for tryptophan degradation pathway is upregulated in the skin lesions of patients with atopic dermatitis or psoriasis.
BACKGROUND
Atopic dermatitis (AD) and psoriasis are common inflammatory skin diseases. Although many reports implicate Th2 cytokines in the pathophysiology of AD and Th1 cytokines in psoriasis, the precise etiology of these diseases remains elusive.


OBJECTIVE
We investigated novel AD- or psoriasis-related genes to further understand the pathogenesis of these diseases.


METHODS
We performed a comprehensive analysis of mRNA expression in skin biopsies from AD or psoriasis patients using DNA microarrays. Quantitative PCR was then used to monitor the expression of novel disease-related genes in human keratinocytes or pinnae from NC/Nga mice.


RESULTS
Levels of mRNA for IDO (indoleamine 2,3-dioxygenase) and kynureninase, enzymes constituting the tryptophan degradation pathway, were found to be upregulated in the skin lesions as compared to the uninvolved skin of patients with AD or psoriasis. Expression of these two genes was induced in human epidermal keratinocytes stimulated with IFN-gamma in vitro. Moreover, in NC/Nga mice, the expression of kynureninase mRNA in the ear skin was induced following development of AD-like skin lesions.


CONCLUSIONS
The tryptophan degradation pathway may play an important role in the pathophysiology of AD and psoriasis.
Ito
Mikito
M
Genox Research Inc., Ibaraki, Japan.
Ogawa
Kaoru
K
Takeuchi
Kaori
K
Nakada
Akiko
A
Heishi
Masayuki
M
Suto
Hajime
H
Mitsuishi
Kouichi
K
Sugita
Yuji
Y
Ogawa
Hideoki
H
Ra
Chisei
C
D000328:Adult; D000818:Animals; D002478:Cells, Cultured; D003876:Dermatitis, Atopic / Q000378:metabolism / Q000503:physiopathology*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology; D006801:Humans; D006867:Hydrolases / Q000235:genetics*; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007371:Interferon-gamma / Q000235:genetics / Q000494:pharmacology; D018793:Interleukin-13 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008875:Middle Aged; D011565:Psoriasis / Q000378:metabolism / Q000503:physiopathology*; D012333:RNA, Messenger / Q000032:analysis; D014364:Tryptophan / Q000378:metabolism*; D014366:Tryptophan Oxygenase / Q000235:genetics*; D015854:Up-Regulation / Q000276:immunology
D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D018793:Interleukin-13; D012333:RNA, Messenger; D015847:Interleukin-4; D007371:Interferon-gamma; D014364:Tryptophan; D014366:Tryptophan Oxygenase; D006867:Hydrolases; C021480:kynureninase