Genomic-scale analysis of psoriatic skin reveals differentially expressed insulin-like growth factor-binding protein-7 after phototherapy.
BACKGROUND
Phototherapy is an effective therapy for psoriasis. The molecular mechanisms underlying its efficacy are not yet understood.


OBJECTIVE
To compare the expression profiles of psoriatic epidermis in patients before and after undergoing phototherapy with the purpose of expounding the molecular mechanisms underlying the efficacy of this therapeutic modality.


METHODS
Patients with psoriasis were investigated before and after full courses of phototherapy: three patients completed 3 weeks of heliotherapy at the Dead Sea; three patients received narrowband ultraviolet B (NB-UVB) for a total of 20-27 treatments. Epidermal samples were analysed using oligonucleotide microarrays. Our microarray results led us to explore further and to quantify a specific gene, insulin-like growth factor-binding protein-7 (IGFBP7), using real-time quantitative reverse transcriptase-polymerase chain reaction assays and immunohistochemical protein expression.


RESULTS
We identified 315 genes modulated by phototherapy: the expressions of 248 genes (142 up; 106 down) were changed by Dead Sea treatment, 116 (71 up; 45 down) by NB-UVB and 49 (37 up; 12 down) were modulated regardless of treatment. The differentially changed genes include S100 calcium-binding proteins, dendritic cell markers, tumour necrosis factor-alpha target genes, matrix metalloproteinases and NFkappaB target genes. We also found that IGFBP7 mRNA and protein were significantly underexpressed in psoriatic compared with normal epidermis, and that phototherapy significantly increased their expression.


CONCLUSIONS
IGFBP7 is underexpressed in psoriatic epidermis but is inducible by UVB.
Hochberg
M
M
Department of Dermatology, Hadassah Hebrew University Medical School, IL-91010 Jerusalem, Israel. malka@hadassah.org.il
Zeligson
S
S
Amariglio
N
N
Rechavi
G
G
Ingber
A
A
Enk
C D
CD
D000328:Adult; D003713:Dendritic Cells / Q000378:metabolism; D004817:Epidermis / Q000528:radiation effects*; D015870:Gene Expression / Q000528:radiation effects; D006801:Humans; D007150:Immunohistochemistry; D018969:Insulin-Like Growth Factor Binding Proteins / Q000378:metabolism*; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D010789:Phototherapy; D011565:Psoriasis / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D009418:S100 Proteins / Q000235:genetics; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014466:Ultraviolet Rays
D018969:Insulin-Like Growth Factor Binding Proteins; D016328:NF-kappa B; D009418:S100 Proteins; D014409:Tumor Necrosis Factor-alpha; D020782:Matrix Metalloproteinases