Neutrophilic inflammation (NI) is a poorly known process occurring in the obese lung that may determine many obesityassociated metabolic abnormalities, including insulin resistance (IR). At sites of NI myeloperoxidase (MPO) oxidizes chloride anions to hyp

DELLA VEDOVA MC; RAMIREZ DC; ALVAREZ, S.; MUNOZ, MD; GOMEZ-MEJIBA S.E

MAR DEL PLATA

Congreso; SAIC; 2016

Macrophages are tissue cells from the innate-immune systemwhere they play a number of homeostatic and defense functions.Inside the tissues and under tissue-specific microenvironmentalpressures monocytes are recruited and differentiated to specificphenotypes. This phenotype is a consequence of the expressionofspecific genes that are under the control of one or more transcription factors.In this context, inflammatory phenotype of adiposetissue (AT) macrophages (ATM-M1) is responsible for adiposetissue oxidative stress and inflammation mediators that reducewhole-body insulin sensitivity and cause a number of metabolicabnormalities-associated to obesity. Intratracheal instillation ofthe nitrone spin trap 5,5-dimethyl-1-pirroline N-oxide (DMPO) todiet-induced obese-mice reduced markers of AT oxidative stressand inflammation, reduced serum concentration of inflammatorycytokines and improved insulin sensitivity. Thus we hypothesizedthat DMPO may produce transcripcional effects in macrophages atthe AT and maybe other tissues. To approach this hypothesis wedetermined the transcripcional effects of DMPO in RAW264.7 cellsafter 6h incubation and with or without lipopolysaccharide (LPS)to model transcriptional profile of ATM. Microarray data showedthat LPS caused an M1-transcriptional pattern, whereas DMPOinhibited these changes. Remarkable effects were observed inthe expression of IRF-7 and PPAR-d, master regulators of genesthat determine M1 and M2 macrophage phenotype. LPS inducedIRF-7, but reduced PPAR-d expression; whereas DMPO reducedIRF-7, but induced PPAR-d expression. Taking together our datasuggest that DMPO may serve as a structural platform for thedesign of novel compounds to reduce AT inflammation and, thusother inflammatory abnormalities-associated to obesity, such asinsulin resistance and metabolic syndrome. Supported by PROICO2-3214 & PICT-2014-3369 (to DCR), PROICO 10-0414 (To SEGM)and PIP2015-2017-112215-0100603CO (To DCR, SEA & SEGM