title: Rifampicin improves neuronal apoptosis in LPS-stimulated co‑cultured BV2 cells through inhibition of the TLR-4 pathway.
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.
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong 510632, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Bi
authors.affiliation: Department of Pathophysiology, Institute of Brain Research, School of Medicine, Jinan University, Guangzhou, Guangdong 510632, P.R. China.
authors.forename: Lihong
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Department of Neurology, Sun Yat‑sen Μemorial Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510120, P.R. China.
authors.forename: Xiuna
authors.initials: X
authors.lastname: Jing
authors.affiliation: Department of Neurology, Sun Yat‑sen Μemorial Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510120, P.R. China.
authors.forename: Zhifen
authors.initials: Z
authors.lastname: Zeng
authors.affiliation: Department of Neurology, Sun Yat‑sen Μemorial Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510120, P.R. China.
authors.forename: Yanran
authors.initials: Y
authors.lastname: Liang
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong 510632, P.R. China.
authors.forename: Anding
authors.initials: A
authors.lastname: Xu
authors.affiliation: Department of Neurology, Sun Yat‑sen Μemorial Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510120, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Neurology, Sun Yat‑sen Μemorial Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510120, P.R. China.
authors.forename: Songhua
authors.initials: S
authors.lastname: Xiao
authors.affiliation: Department of Neurology, Sun Yat‑sen Μemorial Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510120, P.R. China.
authors.forename: Lianhong
authors.initials: L
authors.lastname: Yang
authors.affiliation: Center for Inherited Cardiovascular Disease, Division of Cardiovascular Medicine, Stanford University, School of Medicine, Stanford, CA 94304, USA.
authors.forename: Qiaoyun
authors.initials: Q
authors.lastname: Shi
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong 510632, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Guo
authors.affiliation: Department of Neurology, Sun Yat‑sen Μemorial Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510120, P.R. China.
authors.forename: Enxiang
authors.initials: E
authors.lastname: Tao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002478:Cells, Cultured; D018920:Coculture Techniques; D008070:Lipopolysaccharides / Q000633:toxicity; D051379:Mice; D017628:Microglia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D012293:Rifampin / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D008070:Lipopolysaccharides; D016328:NF-kappa B; D018696:Neuroprotective Agents; D051197:Toll-Like Receptor 4; D012293:Rifampin