Electronic Poster | Session 2

043 – EFFECTS OF ADRENERGIC SIGNALING ON MACROPHAGE ACTIVITY

Beatriz Marton Freire (1) – Juliana Terzi Maricato (1) – Alexandre Salgado Basso (1)
Federal University of São Paulo, Immunology Division, EPM, São Paulo, Brazil (1)

Introduction: The ability of the nervous system to modulate immune responses is well known. It happens, for example, through activation of adrenergic receptors (AR) on immune cells such as macrophages (MO). MO is an evolutionarily conserved cell type; its effector functions are diverse and includes orchestration of inflammation and promotion of tissue repair. Methods: Macrophages were differentiated in vitro from bone marrow progenitor cells. For activation of AR in macrophages, cells were treated with 1 micromolar of a Beta2 AR (B2AR) specific agonist 15 minutes prior to stimulation with 500 microgram of LPS plus 1 nanogram of IFN-gamma. Transcripts were measured by RT-qPCR assay, the production of cytokines was measured using ELISA and the expression of cell surface molecules was analyzed by flow cytometry. Results: Analysis of relative gene expression showed that treatment with the B2AR specific agonist, prior to stimulation with LPS+IFN-gamma, decreased the expression of pro-inflammatory genes, such as Inos, Il12p35, Il12p40, Tnfa and Il6. Additionally, activation of B2AR promotes increase in the gene expression of Arg1. Accordingly, the amount of IL6, TNF-alfa and nitric oxide (NO) produced by MO treated with B2AR agonist was also decreased. Macrophages were treated with noradrenaline, an endogenous ligand of B2AR and the decrease in IL6, TNF-alfa and NO was also observed. Blockage of PKA and EPAC, which are proteins known to participate in the signaling pathway of B2AR, did not revert the downregulation of IL6 and TNF-alfa production and secretion. However, it was not observed difference in the expression of activation markers (CD80/CD86, MHCII and CCR2) on macrophages after B2AR activation. Moreover, activation of B2AR did not affect phagocytosis activity in macrophages. Conclusions: We found that activation of B2AR could modulate macrophage activity, promoting downregulation of genes and proteins linked to a pro inflammatory response. This modulation is independent of EPAC and PKA. Financial Support: FAPESP; CAPES