INQUISAL   20936
INSTITUTO DE QUIMICA DE SAN LUIS "DR. ROBERTO ANTONIO OLSINA"
Unidad Ejecutora - UE
artículos
Título:
The Nitrone Spin Trap 5,5-Dimethyl-1-pyrroline N-oxide prevents M1-like Phenotypic Switch of Lipopolysaccharide-Primed Macrophages
Autor/es:
DELLA VEDOVA MC; DARIO C RAMIREZ; MARCOS D MUNOZ; SANDRA E GOMEZ MEJIBA
Revista:
The Pharmaceutical and Chemical Journal, 2018, 5(2):1-8
Editorial:
CODEN(USA): PCJHBA
Referencias:
Año: 2018 vol. 5 p. 1 - 8
ISSN:
2349-7092
Resumen:
Abstract M1-like inflammatory phenotype of macrophages plays a critical role in tissue damage in chronicinflammatory diseases. M1-like macrophages produce reactive oxygen species, inflammatory cytokines (IL-1b, IFNb),express inflammatory protein such as nitric oxide synthase (iNOS) and surface markers such as CD80; CD86;CD14; CD44. Because M1-like activation contributes to inflammation, decoding its mechanism may lead to findnovel therapies. The nitrone spin trap DMPO reacts with free radicals to form adducts, thus reducing its chainreactions. Our studies have shown that DMPO has also anti-inflammatory effects that may not be related to its freeradical trapping properties. Herein, we hypothesize that DMPO can reduce LPS-induced M1-like activation ofmacrophages by changing its transcriptome and proteome. To test this hypothesis we incubated RAW 264.7 cellswith 1 ng/ml LPS in the presence or absence of 50 mM DMPO for 6h or 24h. Cells were used for the mRNAdetection of M1-phenotypic molecular markers. Transcriptomic analyses are consistent with DMPO preventing theinflammatory M1-like of macrophages by reducing surface markers, inflammatory molecules and type-1 interferonsignaling. To corroborate these data we used western-blots for IRF7 protein expression and ELISA technique forIFN-b1 determination. DMPO-reduced IFN-b1 production and IRF7 expression, whereas increased hemoxygenase-1expression and restores PPARδ expression. Taken together our results indicate that DMPO prevents LPS-triggeredM1-like phenotypic switch of macrophages. Our studies provide critical data for further studies on the possible useof DMPO as a structural platform for the design of novel mechanism-based anti-inflammatory drugs.