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

Abstract

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.

Latent TGFβ1 overexpression in keratinocytes results in a severe psoriasis-like skin disorder

“…In addition to inflammatory cells, fibroblasts in transgenic skin may greatly contribute to epidermal hyperproliferation. It has been shown that psoriatic fibroblasts induce hyperproliferation of normal keratinocytes (Miura et al , 2000). Among fibroblast‐produced growth factors, KGF and IGF‐1 directly stimulate keratinocyte hyperproliferation (Miura et al , 2000).…”

Immunohistochemical analysis of keratinocyte growth factor and fibroblast growth factor 10 expression in psoriasis

“…In fact, the number of cell nuclei positively stained for the Ki‐67 marker appears to correlate with the growth factor expression, which testifies a causative relationship between growth factor secretion in the dermis and proliferation of the epidermis. Similarly, psoriatic fibroblasts induce hyperproliferation of normal keratinocytes in skin equivalent model and express significantly higher insulin‐like growth factor 1 mRNA than control cells (3) .…”

Transcriptional Regulation of Insulin-like Growth Factor-I by Interferon-γ Requires STAT-5b

“…In human umbilical vein endothelial cells, interleukin-1 (IL-1) was shown to induce a transient transcriptional 4.5-fold up-regulation of IGF-I (18), but the mechanism(s) was not demonstrated. In another study, primary dermal fibroblasts were used to investigate the effects of IFN-␥ on IGF-I mRNA expression (19). No regulation was detected, but the study was complicated by the presence of excess fetal bovine serum (10%) in the experimental conditions.…”