Effects of 5,5-dimethyl-1-pyrroline N-oxide (DMPO) eon M1-like macrophages activation: implications on the control of adiposite tissue inflammation

MUÑOZ, MD; DELLA-VEDOVA MC; GERMANO GARCIA MARIA JOSE; RINALDI TOSI MC; ALVAREZ SE; GOMEZ MEJIBA SE; RAMIREZ DC

San Luis

Otro; XXXII Reunión Anual de la Sociedad de Biología de Cuyo; 2014

Sociedad de Biología de Cuyo

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 and it is infiltrated by inflammatory macrophages (M1-like). M1-like AT macrophages (ATM) produce reactive oxygen species and express inflammatory genes like 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 its 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. Cell were then used for transcriptomics (microarray) analyses. Bioinformatic analyses are consistent with DMPO inducing an anti-inflamatory 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 M2-like marker. DMPO-reduced NO production and iNOS expression, whereas increased hemoxygenase-1 expression. Taken together 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 reduce obesity associated co-morbidities