Soluble receptor for advanced glycation end-products enhanced the production of IFN-[gamma] through the NF-[kappa]B pathway in macrophages recruited by ischemia/reperfusion

• Published in: International journal of molecular medicine 2019-06, Vol.43 (6), p.2507
• Main Authors: Zhang, Xiuling, Cao, Xianxian, Dang, Mengqiu, Wang, Hongxia, Chen, Buxing, Du, Fenghe, Li, Huihua, Zeng, Xiangjun, Guo, Caixia
• Format: Article
• Language: English
• Subjects: Care and treatment; Fluorescent antibody technique; Genetic aspects; Heart diseases; Immunohistochemistry; Macrophages
• ISSN: 1107-3756
• DOI: 10.3892/ijmm.2019.4152

The current study investigated the role of sRAGE in the production of IFN-[gamma] 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 5-BrdU incorporation assay. Differentiation of macrophages was detected via immunofluorescence staining of iNOS (M1 macrophage marker). IFN-[gamma] production, due to sRAGE stimulation, in Raw 264.7 macrophages and the NF-[kappa]B signaling pathway were measured using western blotting. A ChIP assay was used to examine the interactions between NF-[kappa]B and the promoter of IFN-[gamma]. The results showed that the number of macrophages in I/R-treated 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. IFN-[gamma] expression in Raw 264.7 macrophages was suppressed by an NF-[kappa]B inhibitor (Bay117082) but enhanced by sRAGE, with or without I/R treatment. Furthermore, sRAGE increased the phosphorylation of I[kappa]B, IKK and NF-[kappa]B, as well as the translocation of NF-[kappa]B into the nucleus of Raw 264.7 macrophages, with or without I/R treatment. ChIP results showed that sRAGE promoted NF-[kappa]B binding to the promoter of IFN-[gamma] 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 IFN-[gamma] through activating the NF-[kappa]B signaling pathway.