Dopamine Agonists Upregulate IL-6 and IL-8 Production in Human Keratinocytes

Abstract

<b><i>Aim:</i></b> 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). <b><i>Methods:</i></b> Cells were stimulated with dopamine and the D<sub>2</sub> 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. <b><i>Results:</i></b> 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. <b><i>Conclusions:</i></b> 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.

Differential Response of Dopamine Mediated by β-Adrenergic Receptors in Human Keratinocytes and Macrophages: Potential Implication in Wound Healing

“…The stimulatory effect of dopamine on the secretion of IL-8 was partially reversed by the β-adrenergic blocker propranolol, similar to the effect previously described in keratinocytes, where dopamine stimulated the production of IL-6 and IL-8 mainly mediated by β-ARs [5]. …”

“…We then analyzed whether the dopamine-induced production of IL-8 was mediated by β-AR, as we previously described for keratinocytes [5]. While 1 × 10 –5 M propranolol did not modify the IL-8 levels, the treatment with the β-adrenergic antagonist significantly reduced the IL-8 production induced by 1 × 10 –5 M dopamine in THP-1 macrophages (Fig.…”

“…In human keratinocytes, we have previously demonstrated that dopamine agonists stimulate the secretion of IL-6 and IL-8, acting on β-ARs and dopaminergic receptors as well as by an oxidative mechanism [5]. In the present study, we have assessed the effect of dopamine mediated by β-ARs in human keratinocytes and macrophages and the potential implication in the wound-healing process.…”

“…It has been demonstrated that dopamine and catecholamines, adrenaline and noradrenaline, modulate proliferation, apoptosis, and cytokine production in immune cells [3, 4]. Both dopaminergic, α- and β-adrenergic receptors (ARs), and intracellular oxidative mechanisms are involved in these processes [4, 5]. …”

m6a RNA Methylation: The Implications for Health and Disease

“…These receptors are considered to be more important for the modulation of T lymphocyte function than D1-like DA receptors [67], this indicates a greater degree of control over T lymphocytes may be exerted by the m 6 A modification and its machinery than had previously been thought possible. Dopamine has also been shown to upregulate interleukin (IL)-6 and IL-8 in keratinocytes [68], indicating a broader control over inflammation. D2-like receptors have been demonstrated to exhibit an influence over chronic neuroinflammation [69] which implicates the m 6 A modification in neurodegeneration and its associated disorders.…”