Rifampicin improves neuronal apoptosis in LPS-stimulated co‑cultured BV2 cells through inhibition of the TLR-4 pathway

Bi,Wei; Zhu,Lihong; Jing,Xiuna; Zeng,Zhifen; Liang,Yanran; Xu,Anding; Liu,Jun; Xiao,Songhua; Yang,Lianhong; Shi,Qiaoyun; Guo,Li; Tao,Enxiang

doi:10.3892/mmr.2014.2480

Rifampicin improves neuronal apoptosis in LPS-stimulated co‑cultured BV2 cells through inhibition of the TLR-4 pathway

Authors:
- Wei Bi
- Lihong Zhu
- Xiuna Jing
- Zhifen Zeng
- Yanran Liang
- Anding Xu
- Jun Liu
- Songhua Xiao
- Lianhong Yang
- Qiaoyun Shi
- Li Guo
- Enxiang Tao
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Affiliations: Department of Neurology, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong 510632, P.R. China, Department of Pathophysiology, Institute of Brain Research, School of Medicine, Jinan University, Guangzhou, Guangdong 510632, P.R. China, Department of Neurology, Sun Yat‑sen Μemorial Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510120, P.R. China, Center for Inherited Cardiovascular Disease, Division of Cardiovascular Medicine, Stanford University, School of Medicine, Stanford, CA 94304, USA
Published online on: August 11, 2014 https://doi.org/10.3892/mmr.2014.2480
Pages: 1793-1799
Copyright: © Bi et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Agents inhibiting microglial activation are attracting attention as candidate drugs for neuroprotection in neurodegenerative diseases. Recently, researchers have focused on the immunosuppression induced by rifampicin. Our previous study showed that rifampicin inhibits the production of lipopolysaccharide (LPS)-induced pro‑inflammatory mediators and improves neuron survival in inflammation; however, the mechanism through which rifampicin inhibits microglial inflammation and its neuroprotective effects are not completely understood. In this study, we examined the effects of rifampicin on morphological changes induced by LPS in murine microglial BV2 cells. Then we investigated, in BV2 microglia, the effects of rifampicin on two signaling pathway componentss stimulated by LPS, the Toll‑like receptor-4 (TLR-4) and the nuclear factor-κB (NF-κB). In addition, we co-cultured BV2 microglia and neurons to observe the indirect neuroprotective effects of rifampicin. Rifampicin inhibited LPS-stimulated expression of the TLR-4 gene. When neurons were co-cultured with LPS-stimulated BV2 microglia, pre-treatment with rifampicin increased neuronal viability and reduced the number of apoptotic cells. Taken together, these findings suggest that rifampicin, with its anti-inflammatory properties, may be a promising agent for the treatment of neurodegenerative diseases.

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