DMPO PREVENTS ENDOTOXIN-INDUCED M1-PHENOTYPE IN MACROPHAGES

AGÜERO CA; RAMIREZ, DC; DELLA-VEDOVA MC; GOMEZ MEJIBA, SE; MUÑOZ MD,; ALVAREZ SE

MZA

Congreso; SBC; 2016

AnM1-Inflammatory phenotype of adipose tissue (AT) macrophages (ATM-M1) isresponsible for adipose tissue oxidative stress and inflammation, which cause anumber of metabolic abnormalities-associated to obesity. Intratrachealinstillation of the nitrone spin trap 5,5-dimethyl-1-pirroline N-oxide (DMPO) to diet-inducedobese-mice reduced markers of AT oxidative stress and inflammation, reducedserum concentration of inflammatory cytokines and improved insulin sensitivity.Thus we hypothesized that DMPO may prevent ATM-M1 phenotype in macrophages. To testthis hypothesis we determined the transcripcional effects of DMPO in RAW264.7cells after 6h incubation and with or without lipopolysaccharide (LPS), as aninductor of an M1 phenotype, to model transcriptional profile of ATM in theobese adipose tissue. Microarray data showed that LPS caused anM1-transcriptional pattern, whereas DMPO reduced these changes. Remarkableeffects were observed in the expression of IRF-7 and PPAR-d, two masterregulators of genes that determine M1 and M2 macrophage phenotype, respectively.LPS induced IRF-7, but reduced PPAR-dexpression; whereas DMPO reduced IRF-7, but induced PPAR-dexpression. Taking together our data suggest that DMPO may serve as astructural platform for the design of novel compounds to reduce AT inflammationand, thus other inflammatory abnormalities-associated to obesity, such asinsulin resistance and metabolic syndrome. Supported by PROICO 2-3214 & PICT-2014-3369 (to DCR), PROICO 10-0414(To SEGM) and PIP2015-2017-112215-0100603CO (To DCR, SEGM & SEGM).