Untitled

Abstract

The neuropeptides substance P (SP), calcitonin gene-related peptide (CGRP) and alpha-melanocyte-stimulating hormone (alpha-MSH) are known to be able to regulate the production of cytokines in the skin. Since IL-8 plays an important role in cutaneous inflammation, the effects of SP, CGRP and alpha-MSH on the IL-8/IL-8 receptor (IL-8RA) systems of these cell types were studied. Cultures of human dermal fibroblasts and an immortalized keratinocyte cell line HaCaT were treated with 10-8 M SP, CGRP or alpha-MSH. The results 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 mRNA 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 expression in HaCaT cells. In contrast, alpha-MSH resulted in a time-dependent induction of the IL-8 mRNA expression in dermal fibroblasts. This induction was already detectable after 6 h, and after 12 h there was a 5-fold change in comparison with the controls. The IL-8 content of the supernatant was also increased, with a maximum at 48 h after alpha-MSH treatment. The data established in the present study support the notion that neuropeptides can directly modulate the IL-8/IL-8RA system of keratinocytes and fibroblasts.

Keratinocyte expression of calcitonin gene-related peptide β: Implications for neuropathic and inflammatory pain mechanisms

“…Various CGRP effects on keratinocytes have been described [60,100,104,106], however direct expression of CGRP among keratinocytes has not been previously reported. We used normal human epidermal keratinocytes (NHEK) grown as monolayer cultures and primary human keratinocytes grown as raft cultures at the air interface, allowing for stratification and formation of an organotypic pseudoepidermis (3D Raft), to further investigate the expression of CGRP in keratinocytes.…”

The neuropeptide Substance P facilitates the transition from an inflammatory to proliferation phase‐associated responses in dermal fibroblasts

“…Previous reports have shown that SP has a pro-proliferative effect on fibroblasts from different species. 22,[54][55][56] However, all these studies have been performed on surfaces with a giga Pascal stiffness, which as we previously observed, is itself sufficient to heighten basal fibroblast activity. Whether SP affects proliferation on substrates that mimic physiological stiffness in an age-dependent manner has not been tested.…”

Roles of calcitonin gene-related peptide in the skin, and other physiological and pathophysiological functions

“…Human dermal fibroblasts move after adding SP to the culture medium ( Kahler et al., 1993a , Kahler et al., 1993b ), and SP upregulates the proliferation of skin fibroblasts ( Morbidelli et al., 1993 ). SP, CGRP, and melanocyte-stimulating hormone (alpha-MSH) can also upregulate the IL-8/IL-8RA system of keratinocytes and fibroblasts ( Kiss et al., 1999 ), important for cutaneous inflammation. CGRP may have a role in fibroproliferation disease (FPD) of the skin ( Akaishi et al., 2008 ).…”