IGF-II is known to induce the growth of keratinocytes and the level was significantly elevated in the tissue fluid of psoriatic lesion. However, the role of IGF-II in psoriasis is not well defined. Because an inflammatory cytokine, interleukin-6 (IL-6) is overexpressed in psoriatic lesions, we explored whether IGF-II has some role in psoriasis through induction of IL-6. Therefore, the expression of IL-6 was analyzed after treatment of IGF-II in primary cultured psoriatic cells and human keratinocyte cell line, HaCaT. We found that IGF-II induced the IL-6 mRNA expression significantly. To investigate the inducing mechanism of IL-6 by IGF-II, we examined the promoter activity of IL-6 and the DNA binding activity of NFkappaB, a strong regulator of IL-6. Interestingly, IL-6 promoter activity and the binding activity of NFkappaB were remarkably increased by IGF-II. Western blot data that IkappaB was reduced by IGF-II significantly suggest that NFkappaB activation by IGF-II may be mediated through the downregulation of IkappaB. Therefore, these results suggest a novel role of IGF-II in psoriasis possibly by inducing IL-6 through the activation of NFkappaB mediated by downregulation of IkappaB.
Copyright 2000 Academic Press.