Soluble receptor for advanced glycation end-products enhanced the production of IFN-γ through the NF-κB pathway in macrophages recruited by ischemia/reperfusion.
Int J Mol Med
; 43(6): 2507-2515, 2019 Jun.
Article
en En
| MEDLINE
| ID: mdl-30942429
ABSTRACT
The current study investigated the role of sRAGE in the production of IFNγ in macrophages with I/R treatment. The number of macrophages in myocardial tissues treated with I/R with or without sRAGE was determined via immunohistochemical staining. Proliferative activity of macrophages was analyzed by a 5BrdU incorporation assay. Differentiation of macrophages was detected via immunofluorescence staining of iNOS (M1 macrophage marker). IFNγ production, due to sRAGE stimulation, in Raw 264.7 macrophages and the NFκB signaling pathway were measured using western blotting. A ChIP assay was used to examine the interactions between NFκB and the promoter of IFNγ. The results showed that the number of macrophages in I/Rtreated myocardial tissues was increased following sRAGE infusion. Proliferation of macrophages was increased significantly in the presence of sRAGE; after I/R treatment, the cells preferred to differentiate into M1 macrophages. IFNγ expression in Raw 264.7 macrophages was suppressed by an NFκB inhibitor (Bay117082) but enhanced by sRAGE, with or without I/R treatment. Furthermore, sRAGE increased the phosphorylation of IκB, IKK and NFκB, as well as the translocation of NFκB into the nucleus of Raw 264.7 macrophages, with or without I/R treatment. ChIP results showed that sRAGE promoted NFκB binding to the promoter of IFNγ in Raw 264.7 macrophages. Therefore, the findings of the present study indicated that sRAGE protected the heart from I/R injuries, which might be mediated by promoting infiltration and the differentiation of macrophages into M1, which would then synthesize and secrete IFNγ through activating the NFκB signaling pathway.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Daño por Reperfusión Miocárdica
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FN-kappa B
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Interferón gamma
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Receptor para Productos Finales de Glicación Avanzada
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Macrófagos
Límite:
Animals
Idioma:
En
Revista:
Int J Mol Med
Asunto de la revista:
BIOLOGIA MOLECULAR
/
GENETICA MEDICA
Año:
2019
Tipo del documento:
Article