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 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.
Kiss
M
M
Department of Dermatology, Albert Szent-Györgyi Medical University, Szeged, Hungary.
Kemény
L
L
Gyulai
R
R
Michel
G
G
Husz
S
S
Kovács
R
R
Dobozy
A
A
Ruzicka
T
T
D015703:Antigens, CD / Q000378:metabolism*; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology*; D002460:Cell Line; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism*; D015603:Keratinocytes / Q000378:metabolism*; D018123:Receptors, Interleukin / Q000378:metabolism*; D023062:Receptors, Interleukin-8A; D015398:Signal Transduction / Q000187:drug effects; D012867:Skin / Q000166:cytology / Q000378:metabolism; D013373:Substance P / Q000494:pharmacology*; D000521:alpha-MSH / Q000494:pharmacology*
D015703:Antigens, CD; D016209:Interleukin-8; D018123:Receptors, Interleukin; D023062:Receptors, Interleukin-8A; D013373:Substance P; D000521:alpha-MSH; D015740:Calcitonin Gene-Related Peptide