title: Rifampicin attenuates rotenone-induced inflammation via suppressing NLRP3 inflammasome activation in microglia.
abstract: A growing body of evidence has supported that environmental factors, such as exposure to heavy metal and pesticides, play an important role in the pathogenesis of Parkinson׳s disease (PD). Rotenone, the active ingredient in various pesticides, has been identified as an inducer of PD. It has been revealed that rotenone induces activation of microglia and generation of pro-inflammatory factors in PD. Our previous studies demonstrated that rifampicin possessed neural protective effect in PD. In this study, we aimed to study the effect of rifampicin on the inflammation induced by rotenone in microglia and the underlying mechanisms. Results demonstrated that rifampicin pretreatment significantly reduced rotenone-induced cytotoxicity and gene expression of IL-1β in BV2 microglia. Moreover, western blot analysis verified that rifampicin pretreatment suppressed NLRP3 inflammasome activation via inhibiting caspase-1 cleavage and protein expression of NLRP3. As it is indicated that reactive oxidative stress (ROS) is one of the activators for NLRP3 inflammasome, we further employed 2',7'-Dichlorodihydrofluorescein diacetate (DCFH-DA) staining and Rhodamine123 staining to detect intracellular ROS and mitochondrial membrane potential (MMP), respectively. Results confirmed that rifampicin obviously reduced intracellular ROS and reversed loss of MMP in BV2 cells treated by rotenone. Taken together, our data indicate that rifampicin pretreatment inhibits maturation of IL-1β and neuroinflammation induced by rotenone via attenuating NLRP3 inflammasome activation. Rifampicin might emerge as a promising candidate for modulating neuroinflammation in PD.
authors.affiliation: Department of Neurology, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, No. 107, West Yanjiang Road, Guangzhou 510120, China; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China. Electronic address: xiaoquezizi@163.com.
authors.forename: Yanran
authors.initials: Y
authors.lastname: Liang
authors.affiliation: Department of Neurology, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, No. 107, West Yanjiang Road, Guangzhou 510120, China.
authors.forename: Xiuna
authors.initials: X
authors.lastname: Jing
authors.affiliation: Department of Neurology, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, No. 107, West Yanjiang Road, Guangzhou 510120, China.
authors.forename: Zhifen
authors.initials: Z
authors.lastname: Zeng
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Jinan University, No. 613, West Huangpu Road, Guangzhou 510630, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Bi
authors.affiliation: Department of Neurology, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, No. 107, West Yanjiang Road, Guangzhou 510120, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Neurology, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, No. 107, West Yanjiang Road, Guangzhou 510120, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Neurology, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, No. 107, West Yanjiang Road, Guangzhou 510120, China.
authors.forename: Lianhong
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Neurology, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, No. 107, West Yanjiang Road, Guangzhou 510120, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Neurology, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, No. 107, West Yanjiang Road, Guangzhou 510120, China.
authors.forename: Songhua
authors.initials: S
authors.lastname: Xiao
authors.affiliation: Department of Neurology, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, No. 107, West Yanjiang Road, Guangzhou 510120, China.
authors.forename: Shuqiong
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Neurology, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, No. 107, West Yanjiang Road, Guangzhou 510120, China.
authors.forename: Danyu
authors.initials: D
authors.lastname: Lin
authors.affiliation: Department of Neurology, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, No. 107, West Yanjiang Road, Guangzhou 510120, China; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China. Electronic address: taoenxiang@163.com.
authors.forename: Enxiang
authors.initials: E
authors.lastname: Tao
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000978:Antiparkinson Agents / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism*; D020170:Caspase 1 / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects / Q000502:physiology; D017628:Microglia / Q000187:drug effects* / Q000502:physiology; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D015213:Neuroimmunomodulation / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism; D012293:Rifampin / Q000494:pharmacology*; D012402:Rotenone / Q000633:toxicity*
chemical_list: D000893:Anti-Inflammatory Agents; D000978:Antiparkinson Agents; D002352:Carrier Proteins; C508585:IL1B protein, human; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D012402:Rotenone; D020170:Caspase 1; D012293:Rifampin
keywords: Microglia; Oxidative stress; Parkinson׳s disease; Rifampicin; Rotenone