Author:
Jeon Hui-Jeon,Byun Jun-Kyu,Lee Sang Bong,Son Kwang Hee,Lim Ji-Youn,Lee Da Sol,Kim Kil Soo,Park Jin Woo,Shin Gyeong Rim,Kim Ye Jin,Jin Jonghwa,Kim Daehoon,Kim Dong-Ho,Yu Ji Hoon,Choi Yeon-Kyung,Park Keun-Gyu,Jeon Yong Hyun
Abstract
Abstract
Background
N-methyl-d-aspartate receptors (NMDARs) are considered to be involved in several physiological and pathophysiological processes in addition to the progression of neurological disorders. However, how NMDARs are involved in the glycolytic phenotype of M1 macrophage polarization and the possibility of using them as a bio-imaging probe for macrophage-mediated inflammation remain unclear.
Methods
We analyzed cellular responses to NMDAR antagonism and small interfering RNAs using mouse bone marrow-derived macrophages (BMDMs) treated with lipopolysaccharide (LPS). An NMDAR targeting imaging probe, N-TIP, was produced via the introduction of NMDAR antibody and the infrared fluorescent dye FSD Fluor™ 647. N-TIP binding efficiency was tested in intact and LPS-stimulated BMDMs. N-TIP was intravenously administered to mice with carrageenan (CG)- and LPS-induced paw edema, and in vivo fluorescence imaging was conducted. The anti-inflammatory effects of dexamethasone were evaluated using the N-TIP-mediated macrophage imaging technique.
Results
NMDARs were overexpressed in LPS-treated macrophages, subsequently inducing M1 macrophage polarization. Mechanistically, NMDAR-mediated Ca2+ accumulation resulted in LPS-stimulated glycolysis via upregulation of PI3K/AKT/mTORC1 signaling. In vivo fluorescence imaging with N-TIP showed LPS- and CG-induced inflamed lesions at 5 h post-inflammation, and the inflamed lesions could be detected until 24 h. Furthermore, our N-TIP-mediated macrophage imaging technique helped successfully visualize the anti-inflammatory effects of dexamethasone in mice with inflammation.
Conclusion
This study demonstrates that NMDAR-mediated glycolysis plays a critical role in M1 macrophage-related inflammation. Moreover, our results suggest that NMDAR targeting imaging probe may be useful in research on inflammatory response in vivo.
Funder
National Research Foundation of Korea
Korea National Sport University
Ministry of Health and Welfare
National research foundation of korea
Publisher
Springer Science and Business Media LLC
Subject
General Biochemistry, Genetics and Molecular Biology
Cited by
2 articles.
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