Insulin-like growth factor II induces interleukin-6 expression via NF kappa B activation in psoriasis

IGF-IH is known to induce the growth of keratinocytes and the level was sig nificantly elevated in the tissue fluid of psoriatic lesion. However, the r ole of IGF-II in psoriasis is not well defined. Because an inflammatory cyt okine, interleukin-6 (IL-6) is overexpressed in psoriatic lesions, we explo red whether IG;F-LI has some role in psoriasis through induction of IL-6. T herefore, the expression of IL-6 was analyzed after treatment of IGF-II in primary cultured psoriatic cells and human keratinocyte cell line, HaCaT. W e found that IGF-II induced the IL-6 mRNA expression significantly. To inve stigate the inducing mechanism of IL-6 by IGF-II, we examined the promoter activity of IL-6 and the DNA binding activity of NF kappaB, a strong regula tor of IL-6. Interestingly, IL-6 promoter activity and the binding activity of NF kappaB were remarkably increased by IGF-II. Western blot data that I kappaB was reduced by IGF-II significantly suggest that NF kappaB activati on by IGF-II may be mediated through the downregulation of I kappaB. Theref ore, these results suggest a novel role of IGF-II in psoriasis possibly by inducing IL-6 through the activation of NF kappaB mediated by downregulatio n of I kappaB. (C) 2000 Academic Press.