Dopamine agonists upregulate IL-6 and IL-8 production in human keratinocytes.
OBJECTIVE
Catecholamines regulate functions of the nervous, neuroendocrine and immune systems. Dopamine may modulate the activity of keratinocytes, which play a role in secreting cytokines and chemokines. The aim of this study was to evaluate the effect of dopaminergic agonists on the production of IL-6 and IL-8 by a non-tumoral human keratinocyte cell line (HaCaT).


METHODS
Cells were stimulated with dopamine and the D(2) dopamine receptor agonist cabergoline. Levels of IL-6 and IL-8 in culture supernatants were then determined. Cell proliferation was also assessed. Assays were carried out in the presence or absence of the dopaminergic and β-adrenergic receptor antagonists (sulpiride and propranolol, respectively) and ascorbic acid.


RESULTS
Dopamine stimulated the production of IL-6 and IL-8 in a concentration-dependent manner. The effects observed on the secretion of IL-6 were more potent than those corresponding to IL-8 and were reduced by ascorbic acid. The dopamine-induced IL-6 secretion was partially reduced by sulpiride and abrogated by propranolol. The latter drug was able to block the effect of dopamine on the secretion of IL-8. The cabergoline-induced IL-6 release was reduced by sulpiride. Cell viability was not affected by any of the drugs.


CONCLUSIONS
Dopaminergic agonists can stimulate keratinocytes to produce IL-6 and IL-8 which are related to inflammatory cutaneous processes. These effects are mediated by dopaminergic and β-adrenergic receptors and by receptor-independent oxidative mechanisms.
Instituto de Estudios de la Inmunidad Humoral R.A. Margni (CONICET-UBA), Universidad de Buenos Aires, Buenos Aires, Argentina.
Andrea Cecilia
AC
Parrado
Andrea
A
Canellada
Teresa
T
Gentile
Estela Beatriz
EB
Rey-Roldán
D002460:Cell Line; D018491:Dopamine Agonists / Q000494:pharmacology*; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis*; D016209:Interleukin-8 / Q000096:biosynthesis*; D015603:Keratinocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology*
D018491:Dopamine Agonists; C508600:IL6 protein, human; D015850:Interleukin-6; D016209:Interleukin-8