Immunomodulatory effect of dopamine via β-adrenergic receptors in human keratinocytes and macrophages: implication on wound healing

PARRADO CECILIA; SALAVERRY LUCIANA; MANGONE FRANCO; GENTILE TERESA; CANELLADA ANDREA; REY-ROLDAN ESTELA

Ciudad Autónoma de Buenos Aires

Congreso; IV INTERNATIONAL CONGRESS IN TRANSLATIONAL MEDICINE; 2018

Universidad de Buenos Aires y la Universidad Albert Ludwigs, Alemania

Dopamine is a catecholaminergic neurotransmitter which regulates several functions of the nervous, endocrine and immune systems. In the skin, dopamine would modulate keratinocytes and tissue macrophages activities. These cells are strongly involved in the cutaneous immune system defense. Against external agents, keratinocytes and macrophages of cutaneous immune system produce, pro-inflammatory cytokines and metalloproteinases (MMP), which can participate in wound repair process. The expression of these inflammatory mediators is regulated by several signal transduction pathways, such as the activation of NFκB, which is an important proinflammatory transcription factor expressed in many cell types, including macrophages and keratinocytes. Both cells have catecholaminergic system, which is involved in inflammatory diseases and skin physiological processes (wound healing). Previously, we demonstrated that 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. In this work, we evaluated the effect of dopamine (10-6, 10-5, 10-4M) in the presence/absence of the β-adrenergic antagonist propranolol (10-5M) on wound closure (wound scratch assay), MMP activity (MMP-9, zymography), cytokine production (IL-8, IL-1β, ELISA), IκB/NFκB pathway activation (western blot), in a line of human keratinocyte HaCaT and THP-1 PMA-differentiated macrophages. We previously demonstrated that DA increased IL-6 and IL-8 production by β-adrenergic receptor in human keratinocytes. In this work, we demonstrated that DA (10-5) did not modify the wound closure in keratinocytes, but decreased the propranolol stimulatory effect (p