DIFFERENTIAL RESPONSE OF DOPAMINE MEDIATED BY β-ADRENERGIC RECEPTORS IN HUMAN KERATINOCYTES AND MACROPHAGES: POTENTIAL IMPLICATON IN WOUND HEALING

PARRADO CECILIA; SALAVERRY LUCIANA; MANGONE FRANCO; SOTELO AGUSTINA; APICELA CAROLINA; SACCODOSSI NATALIA; CANELLADA ANDREA; REY-ROLDAN ESTELA

Buenos Aires

Congreso; Reunion conjunta de Sociedades de Biociencias; 2017

Dopamine (DA) is a neurotransmitter modulator of the immunesystem. Against external agents, keratinocytes and macrophages ofthe cutaneous immune system produce pro-inflammatory cytokinesand metalloproteinases (MMP), which are involved in wound healing.Both cells have a catecholaminergic system thought to modulateseveral processes in the skin such as inflammation and tissuerepair. In this work, we evaluated the effect of dopamine (10-6, 10-5,10-4M) in the presence or absence of the β-adrenergic antagonistpropranolol (10-5M) on wound closure (wound scratch assay), MMPactivity (MMP-9, zymography), cytokine production (IL-8, IL-1β, ELISA),IκB/NFκB pathway activation (western blot), in a cell line ofhuman keratinocytes HaCaT and THP-1 macrophages (PMA-differentiatedcells). We previously demonstrated that DA increased IL-6and 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 stimulatoryeffect (p<0.05) delaying the cell migration. MMP-9 activity(p<0.001) and propranolol-induced MMP9 activity were decreasedby DA (p<0.05). In addition, DA (10-5) increase NFκB-p65 levels innuclear extracts (p<0.01), this effect was reduced in presence ofpropranolol (p<0.05), suggesting NFκB pathway is involved in theeffect of DA on keratinocytes. On the other hand, DA (10-5) increasedMMP-9 activity (p<0.01) without affecting the propranolol-inducedMMP-9 activity in THP-1 macrophages. DA increased IL-8 production(p<0.01), effect that was reduced in presence of propranolol(p<0.05). However, DA did not modify NFκB-p65 in nuclear extracts,evidencing the latter pathway is not implicated in the effect of DA inhuman macrophages. In conclusion, these results suggest a differentialeffect of DA, via β-adrenergic receptors, that depends on thephysiological condition and the cell type involved that could affectthe wound healing process.