Artículo
The Nitrone Spin Trap 5,5-Dimethyl-1-pyrroline N-oxide prevents M1-like Phenotypic Switch of Lipopolysaccharide-Primed Macrophages
Fecha de publicación:
06/2018
Editorial:
Pharmaceutical and Chemical Journal
Revista:
Pharmaceutical and Chemical Journal
ISSN:
2349-7092
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
M1-like inflammatory phenotype of macrophages plays a critical role in tissue damage in chronic inflammatory 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 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 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 6h or 24h. Cells were used for the mRNA detection of M1-phenotypic molecular markers. Transcriptomic analyses are consistent with DMPO preventing the inflammatory M1-like of macrophages by reducing surface markers, inflammatory molecules and type-1 interferon signaling. To corroborate these data we used western-blots for IRF7 protein expression and ELISA technique for IFN-b1 determination. DMPO-reduced IFN-b1 production and IRF7 expression, whereas increased hemoxygenase-1 expression and restores PPARδ expression. Taken together our results indicate that DMPO prevents LPS-triggered M1-like phenotypic switch of macrophages. Our studies provide critical data for further studies on the possible use of DMPO as a structural platform for the design of novel mechanism-based anti-inflammatory drugs.
Palabras clave:
DMPO
,
INFLAMMATION
,
LIPOPOLYSACCHARIDE
,
MACROPHAGE
,
TRANSCRIPTOMICS
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Articulos(IMIBIO-SL)
Articulos de INST. MULTIDICIPLINARIO DE INV. BIO. DE SAN LUIS
Articulos de INST. MULTIDICIPLINARIO DE INV. BIO. DE SAN LUIS
Articulos(INQUISAL)
Articulos de INST. DE QUIMICA DE SAN LUIS
Articulos de INST. DE QUIMICA DE SAN LUIS
Citación
Muñoz, Marcos David; Della Vedova, Maria Cecilia; Gomez-Mejiba, Sandra Esther; Ramirez, Dario; The Nitrone Spin Trap 5,5-Dimethyl-1-pyrroline N-oxide prevents M1-like Phenotypic
Switch of Lipopolysaccharide-Primed Macrophages; Pharmaceutical and Chemical Journal; Pharmaceutical and Chemical Journal; 5; 2; 6-2018; 1-8
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