Involvement of insulin-like growth factor-I in psoriasis as a paracrine growth factor: dermal fibroblasts play a regulatory role in developing psoriatic lesions.
To investigate the contribution of dermal fibroblasts to the development of psoriasis, we examined the expression of mRNA for insulin-like growth factor-I (IGF-I) and its regulator IGF-I binding proteins (IGFBPs) in psoriatic fibroblasts by RT-PCR. We also studied the effect of inflammatory cytokines including interferon gamma (IFN-gamma), tumor necrosis factor alfa (TNF-alpha), and IFN-alpha on the expression of IGF-I and IGFBPs in the fibroblasts. Semiquantitative analysis revealed that IGF-I mRNA expression in psoriatic fibroblasts (PF) was significantly higher than in control fibroblasts (CF). However, no significant difference in IGF-I mRNA was shown between nonlesional psoriatic fibroblasts (NF) and CF. Treatment with IFN-alpha in vitro upregulated IGF-I mRNA in PF and in CF. TNF-alpha appeared to downregulate IGF-I mRNA in PF but had no effect on CF. IFN-gamma did not show a significant effect on IGF-I mRNA levels in any type of fibroblast. IGFBP-3 mRNA was expressed equally in PF and CF, and was not affected by cytokines. The expression of IGFBP-5 mRNA in PF was downregulated by IFN-gamma and TNF-alpha. Taken together, these results indicate that dermal fibroblasts may contribute to the epidermal hyperplasia of psoriasis by promoting keratinocyte proliferation through IGF-I, whose secretion could be modulated by inflammatory cytokines.
Miura
H
H
Department of Dermatology, Course of Molecular Medicine, Graduate School of Medicine, Osaka University, Yamadaoka, Japan.
Sano
S
S
Higashiyama
M
M
Yoshikawa
K
K
Itami
S
S
D000293:Adolescent; D000328:Adult; D018929:Cell Culture Techniques; D016207:Cytokines / Q000494:pharmacology; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins / Q000187:drug effects / Q000235:genetics; D007334:Insulin-Like Growth Factor I / Q000187:drug effects* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D019899:Paracrine Communication; D011565:Psoriasis / Q000209:etiology* / Q000473:pathology; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D016207:Cytokines; D018969:Insulin-Like Growth Factor Binding Proteins; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I