Effects of the neuropeptides substance P, calcitonin gene-related peptide and alpha-melanocyte-stimulating hormone on the IL-8/IL-8 receptor system in a cultured human keratinocyte cell line and dermal fibroblasts

The neuropeptides substance P (SP), calcitonin gene-related peptide (CGRP) and alpha-melanocyte-stimulating hormone (alpha-MSH) are known to be able t o regulate the production of cytokines in the skin. Since IL-8 plays an imp ortant role in cutaneous inflammation, the effects of SP, CGRP and alpha-MS H on the IL-8/IL-8 receptor (IL-8RA) systems of these cell types were studi ed. Cultures of human dermal fibroblasts and an immortalized keratinocyte c ell line HaCaT were treated with 10(-8) M SP. CGRP or alpha-MSH. The result s demonstrated that these neuropeptides have different effects on the IL-8 and IL-8RA expressions of the cells. SP and CGRP upregulated the IL-8RA mRN A expression in HaCaT cells, but had no influence on their IL-8 production, whereas, alpha-MSH had no effect on either the IL-8 or the IL-8RA mRNA exp ression in HaCaT cells. In contrast, or-MSH resulted in a time-dependent in duction of the IL-8 mRNA expression in dermal fibroblasts. This induction w as already detectable after 6 h, and after 12 h there was a 5-fold change i n comparison with the controls. The IL-8 content of the supernatant was als o increased, with a maximum at 48 h after alpha-MSH treatment. The data est ablished in the present study support the notion that neuropeptides can dir ectly modulate the IL-8/IL-8RA system of keratinocytes and fibroblasts.