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Lipopolysaccharide-Induced Microglial Neuroinflammation: Attenuation by FK866

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Abstract

Alleviating microglia-mediated neuroinflammation bears great promise to reduce neurodegeneration. Nicotinamide phosphoribosyltransferase (NAMPT) may exert cytokine-like effect in the brain. However, it remains unclear about role of NAMPT in microglial inflammation. Also, it remains unknown about effect of NAMPT inhibition on microglial inflammation. In the present study, we observed that FK866 (a specific noncompetitive NAMPT inhibitor) dose-dependently inhibited lipopolysaccharide (LPS)-induced proinflammatory mediator (interleukin (IL)-6, IL-1β, inducible nitric oxide synthase, nitric oxide and reactive species) level increase in BV2 microglia cultures. FK866 also significantly inhibited LPS-induced polarization change in microglia. Furthermore, LPS significantly increased NAMPT expression and nuclear factor kappa B (NF-κB) phosphorylation in microglia. FK866 significantly decreased NAMPT expression and NF-κB phosphorylation in LPS-treated microglia. Finally, conditioned medium from microglia cultures co-treated with FK866 and LPS significantly increased SH-SY5Y and PC12 cell viability compared with conditioned medium from microglia cultures treated with LPS alone. Our study strongly indicates that NAMPT may be a promising target for microglia modulation and NAMPT inhibition may attenuate microglial inflammation.

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Data Availability

The datasets analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

This work was supported by the Projects of the National Natural Science Foundation of China [Grant Number 81671273], [Grant Number 81171204], [Grant Number 30772280], [Grant Number 81400925], [Grant Number 81471148], [Grant Number 81771211], [Grant Number 81703852]; the Project of Shanghai Municipal Education Commission of China [Grant Number 14YZ046]; the Project of Shanghai Municipal Health and Family Planning Commission of China [Grant Number 20134049], the Project of Shanghai Jiao Tong University of China [Grant Number YG2013MS22]; the Project of National Eastern Tech-transfer Center [Grant Number 201713972877]; the Projects of Shanghai Committee of Science and Technology [Grant Number 17401901000]; National Key R and D Program of China [Grant Number 2017YFC1310300]; SHSMU-ION Research Center for Brain Disorders [Grant Number 2015NKX007].

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  1. Department of Neurology, Xinhua Hospital Affiliated To Shanghai Jiao Tong University School of Medicine, 1665 Kongjiang Road, Shanghai, 200092, People’s Republic of China

    Yaling Xu, Lijia Yu, Ying Liu, Xiaohui Tang & Xijin Wang

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Xu, Y., Yu, L., Liu, Y. et al. Lipopolysaccharide-Induced Microglial Neuroinflammation: Attenuation by FK866. Neurochem Res 46, 1291–1304 (2021). https://doi.org/10.1007/s11064-021-03267-4

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