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

SALAVERRY, LUCIANA SOLEDAD; GENTILE, TERESA; MANGONE, FRANCO MAURICIO; CANELLADA, ANDREA; PARRADO, ANDREA CECILIA; APICELLA, CAROLINA EUGENIA; REY-ROLDÁN, ESTELA BEATRIZ

NEUROIMMUNOMODULATION.

KARGER

Lugar: Basel; Año: 2018 p. 282 - 291

1021-7401

Objective: Dopamine is an immunomodulatory neurotransmitter. In the skin, keratinocytes and macrophages produce proinflammatory cytokines and metalloproteinases (MMPs) which participate in wound healing. These cells have a catecholaminergic system that modulates skin pathophysiologic processes. We have demonstrated that dopamine modulates cytokine production in keratinocytes via dopaminergic and adrenergic receptors (ARs). The aim of this study was to evaluate the effect of dopamine and its interaction with β-ARs in human HaCaT keratinocytes and THP-1 macrophages. We evaluated the production of inflammatory mediators implicated in wound healing. Methods: Cells were stimulated with dopamine in the absence or presence of the β-adrenergic antagonist propranolol. Wound closure, MMP activity, and the production of IL-8, IL-1β, and IκB/NFκB pathway activation were determined in stimulated cells. Results: Dopamine did not affect the wound closure in human keratinocytes, but diminished the propranolol stimulatory effect, thus delaying cell migration. Similarly, dopamine significantly decreased MMP-9 activity and the propranolol-induced MMP activity. Dopamine significantly increased the p65-NFκB subunit levels in the nuclear extracts, which were reduced in the presence of propranolol in keratinocytes. On the other hand, dopamine significantly increased MMP-9 activity in THP-1 macrophages, but did not modify the propranolol-increased enzymatic activity. Dopamine significantly increased IL-8 production in human macrophages, an effect that was partially reduced by propranolol. Dopamine did not modify the p65-NFκB levels in the nuclear extracts in THP-1 macrophages. Conclusion: We suggest that the effect of dopamine via β-ARs depends on the physiological condition and the cell type involved, thus contributing to either improve or interfere with the healing process.