The production of cytokines induced by breast tumor antigens in dendritic cells is modulated by cholinergic activation.

OROñO, MANUEL; SALES, MARIA ELENA; GIAMBALVO GóMEZ, DILEYVIC; LOMBARDI, GABRIELA; MARTINEZ PULIDO, PAOLA

Melbourne

Congreso; International Congress of Immunology; 2016

Australasian Society for immunology and IUIS

We have previously described the presence of a functional non neuronal cholinergic system in human dendritic cells (DC). The addition of cholinergic agonists, carbachol and acetylcholine modulates the function of DC. Taking into account that a deficiency in the activity of DC was reported in tumor bearers, we investigated the effect of cholinergic receptors (ChR) activation in human DC cells regarding their cytokine profile. Experiments were performed in the absence or presence of tumor antigens obtained from the human luminal breast adenocarcinoma, MCF-7, the most common type of tumor in women. Methods: DC were obtained from human monocytes and were treated during 24h with different concentrations of MCF-7 tumor extract (MTE). Afterwards, DC were stimulated with carbachol during 1 h in the absence or presence of cholinergic antagonists (atropine or mecamylamine). Finally, DC were cultured without or with lipopolysaccharide during 24 h to obtain immature or mature DC (iDC or mDC). The production of cytokines in culture supernatants was quantified by ELISA. Results: in iDC, the addition of increasing doses of MTE triggered a potent up-regulation of interleukin (IL)-10 production while the effect on IL-12 or tumor necrosis factor alfa (TNF-α) levels was less potent (495±19%**;295±28%*; 269±20%*, respectively; **p