Format

Send to

Choose Destination
Molecules. 2019 Jan 21;24(2). pii: E367. doi: 10.3390/molecules24020367.

Effects of Betaine on LPS-Stimulated Activation of Microglial M1/M2 Phenotypes by Suppressing TLR4/NF-κB Pathways in N9 Cells.

Author information

1
Department of Pharmacology, Ningxia Medical University, Yinchuan 750004, China. 15771377892@163.com.
2
Department of Pharmacology, Ningxia Medical University, Yinchuan 750004, China. nomoredrama@126.com.
3
Department of Pharmacology, Ningxia Medical University, Yinchuan 750004, China. quanhongfeng@163.com.
4
Functional Experiment Center, School of Basic Medicine, Ningxia Medical University, Yinchuan 750004, China. Yanlin1@Tom.com.
5
Laboratory in Fertility Preservation and Maintenance of Ministry of Education, Ningxia Medical University, Yinchuan 750004, China. peixy@nxmu.edu.cn.
6
Department of Pharmacology, Ningxia Medical University, Yinchuan 750004, China. pengxd@nxmu.edu.cn.
7
Laboratory in Fertility Preservation and Maintenance of Ministry of Education, Ningxia Medical University, Yinchuan 750004, China. pengxd@nxmu.edu.cn.
8
Department of Pharmacology, Ningxia Medical University, Yinchuan 750004, China. 11119034@zju.edu.cn.
9
Functional Experiment Center, School of Basic Medicine, Ningxia Medical University, Yinchuan 750004, China. 11119034@zju.edu.cn.
10
Laboratory in Fertility Preservation and Maintenance of Ministry of Education, Ningxia Medical University, Yinchuan 750004, China. 11119034@zju.edu.cn.

Abstract

Microglia mediate multiple facets of neuroinflammation. They can be phenotypically divided into a classical phenotype (pro-inflammatory, M1) or an alternative phenotype (anti-inflammatory, M2) with different physiological characteristics and biological functions in the inflammatory process. Betaine has been shown to exert anti-inflammatory effects. In this study, we aimed to verify the anti-inflammatory effects of betaine and elucidate its possible molecular mechanisms of action in vitro. Lipopolysaccharide (LPS)-activated microglial cells were used as an inflammatory model to study the anti-inflammatory efficacy of betaine and explore its mechanism of regulating microglial polarisation by investigating the morphological changes and associated inflammatory changes. Cytokine and inflammatory mediator expression was also measured by ELISA, flow cytometry, immunofluorescence, and western blot analysis. Toll-like receptor (TLR)-myeloid differentiation factor 88 (Myd88)-nuclear factor-kappa B (NF-κB) p65, p-NF-κB p65, IκB, p-IκB, IκB kinase (IKK), and p-IKK expression was determined by western blot analysis. Betaine significantly mitigated the production of pro-inflammatory cytokines and increased the release of anti-inflammatory cytokines. It promoted the conversion of the microglia from M1 to M2 phenotype by decreasing the expression of inducible nitric oxide synthase and CD16/32 and by increasing that of CD206 and arginase-1. Betaine treatment inhibited the TLR4/NF-κB pathways by attenuating the expression of TLR4-Myd88 and blocking the phosphorylation of IκB and IKK. In conclusion, betaine could significantly alleviate LPS-induced inflammation by regulating the polarisation of microglial phenotype; thus, it might be an effective therapeutic agent for neurological disorders.

KEYWORDS:

M1/M2 polarisation; N9 microglial cells; betaine; microglia; neuroinflammation

PMID:
30669620
PMCID:
PMC6359206
DOI:
10.3390/molecules24020367
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Multidisciplinary Digital Publishing Institute (MDPI) Icon for PubMed Central
Loading ...
Support Center