EFFECTS OF 5,5-DIMETHYL-1-PYRROLINE N-OXIDE (DMPO) ON M1-LIKE MACROPHAGE ACTIVATION: IMPLICATIONS ON THE CONTROL OF ADIPOSE TISSUE INFLAMMATION

MUÑOZ MD, DELLA VEDOVA MC, GERMANÓ MJ, RINALDI TOSI MC, ALVAREZ SE, GOMEZ MEJIBA SE, RAMIREZ DC.

San Luis

Congreso; XXXII Reunion Cientifica Anual de la Sociedad de Biologia de Cuyo; 2014

Sociedad Biologia de Cuyo

EFFECTS OF 5,5-DIMETHYL-1-PYRROLINE N-OXIDE (DMPO) ON M1-LIKE MACROPHAGE ACTIVATION: IMPLICATIONS ON THE CONTROL OF ADIPOSE TISSUE INFLAMMATION Muñoz MD, Della-Vedova MC, Germanó MJ, Rinaldi Tosi MC, Alvarez SE, Gomez Mejiba SE, Ramirez DC. Laboratorio de Medicina Experimental y Terapéuticas. IMIBIO-SL-CONICET, UNSL. Email:ramirezlabimibiosl@ymail.com Adipose tissue (AT) inflammation in obesity is a leading cause of systemic inflammation and obesity-associated co-morbidities. The obese AT is metabolically stressed by free fatty acids, lipopolysaccharide (LPS), hypoxia that activate NF-kB-signaling program in macrophages giving them an inflammatory (M1-like) phenotype. M1-like AT macrophages (ATM) produce reactive oxygen species and express inflammatory genes, such as inducible nitric oxide synthase (iNOS). Because ATM M1-like activation is the leading cause of AT inflammation, decoding its mechanism may lead to find novel therapies. The nitrone spin trap DMPO reacts with free radicals to form adducts, thus reducing further chain reactions. Our studies have shown that DMPO has also anti-inflammatory effects that may not be related to its free radical trapping properties. Herein, we hypothesize that DMPO by itself can reduce LPS-induced M1-like activation of macrophages by changing its transcriptome and proteome. To test this hypothesis we incubated RAW 264.7 cells with 1 ng/ml LPS in the presence or absence of 50 mM DMPO for 4h or 24h. Cells were then used for transcriptomics (microarray) and Western blot analyses. Bioinformatics analyses are consistent with DMPO inducing an anti-inflammatory M2-like phenotype of macrophages. To corroborate these data we assessed nitric oxide production, iNOS expression as markers of M1 and hemoxygenase-1 (HO-1) as marker M2-like cells. DMPO-reduced NO production and iNOS expression, whereas increased hemoxygenase-1 expression. Our results indicate that DMPO prevents LPS-triggered M2 to M1 phenotypic switch of macrophages. Further studies on ATM phenotypic switch in obesity will help to find mechanism-based therapies to prevent AT inflammation and thus to reduce obesity associated co-morbidities. EN PRENSA