Involvement of insulin-like growth factor-I in psoriasis as a paracrine growth factor : dermal fibroblasts play a regulatory role in developing psoriatic lesions

• Published in: Archives of Dermatological Research 2000-12, Vol.292 (12), p.590-597
• Main Authors: MIURA, H, SANO, S, HIGASHIYAMA, M, YOSHIKAWA, K, ITAMI, S
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Biological and medical sciences; Cell Culture Techniques; Cytokines - pharmacology; Dermatology; Female; Fibroblasts - metabolism; Humans; Insulin-Like Growth Factor Binding Proteins - drug effects; Insulin-Like Growth Factor Binding Proteins - genetics; Insulin-Like Growth Factor I - drug effects; Insulin-Like Growth Factor I - genetics; Male; Medical sciences; Middle Aged; Paracrine Communication; Psoriasis - etiology; Psoriasis - pathology; Psoriasis. Parapsoriasis. Lichen; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - drug effects; RNA, Messenger - metabolism
• ISSN: 0340-3696; 1432-069X
• DOI: 10.1007/s004030000188

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.