Rifampicin Attenuates Rotenone-Treated Microglia Inflammation via Improving Lysosomal Function
Abstract
Mounting evidence suggests that lysosome dysfunction promotes the progression of several neurodegenerative diseases via hampering autophagy flux. While regulation of autophagy in microglia may affect chronic inflammation involved in Parkinson's disease (PD). Our previous studies have reported rifampicin inhibits rotenone-induced microglia inflammation by enhancing autophagy, however the precise mechanism remains unclear. Human microglia (HM) cells were pretreated with 100 μM rifampicin for 2 h followed by exposure to 0.1 μM rotenone. We found that rifampicin pretreatment suppressed the gene expression of IL-1β and IL-6 via inhibiting activation of JNK after rotenone induction, but the anti-inflammatory effect of rifampicin was reversed by chloroquine. Moreover, rifampicin pretreatment not only improved the ratio of LC3-II/LC3-I in rotenone-treated cells, but also increased autolysosomes and decreased autophagosomes in RFP-GFP-LC3B transfected HM cells exposed to rotenone, thus indicating rifampicin improves autophagy flux in rotenone-treated HM cells. Finally, we verified rifampicin pretreatment enhanced ATP6V0A1 expression when compared to that exposed to rotenone alone. ATP6V0A1 knockdown inhibited the effect of rifampicin on maintaining lysosome acidification and autophagosome-lysosome fusion in rotenone-treated microglia. Taken together, our results indicated that rifampicin attenuates rotenone-induced microglia inflammation partially via elevating ATP6V0A1. Modulation of lysosomal function by rifampicin may be a novel therapeutic strategy for PD.
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Rifampicin sustains cell viability by enhancing autophagy.
“Although not completely defined, rifampicin appears to sustain cell viability through different mechanisms: (i) by enhancing autophagy [293,295]; (ii) via PI3K/Akt/GSK-3β/CREB pathway modulation [296]; (iii) by upregulating the unfolded protein response marker GRP78 through the PERK/eIF2α/ATF4 pathway [297].”
From The Interplay between Gut Microbiota and Parkinson’s Disease: Implications on Diagnosis and Treatment (2022) · cites this paper as [295]
Rifampicin reduces IL-1β, TNF-α, IL-6 and ROS released by cells double treated with rotenone and rifampicin.
“Other studies reported a reduction in IL-1β, TNF-α, IL-6 and ROS released by cells double treated with rotenone and rifampicin, thus indicating a promotion of neuroprotection [293,294,295].”
From The Interplay between Gut Microbiota and Parkinson’s Disease: Implications on Diagnosis and Treatment (2022) · cites this paper as [295]
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- Authors
- Liang, Y., Zheng, D., Peng, S., Lin, D., Jing, X., Zeng, Z., Chen, Y., Huang, K., Xie, Y., Zhou, T., & Tao, E.
- Affiliations
- Sun Yat-sen University (CN)
- First People's Hospital of Foshan (CN)
- Corresponding author
- Zhou, Tianen
- Tao, Enxiang
- Venue
- Toxicology in Vitro
- Publisher
- Elsevier BV
- Published
- 2020-03
- Volume
- 63
- Pages
- 104690
- ISSN
- 0887-2333 (ISSN-L)
- OpenAlex
- W2981452787
- Cited by
- 33
- References
- 32
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 2 · 2023: 8 · 2022: 7 · 2021: 5 · 2020: 4
- FWCI
- 3.04
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Toxicology in Vitro (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Applied Basic Research Foundation of Yunnan Province (2016A030313322)
- Fundamental Research Fund of Shandong University (17ykpy39)
- Key Research and Development Program of Jiangxi Province (2018B030337001)
- Guangzhou Key Laboratory of Malignant Tumor Therapy and Translational Medicine (KLB09001)
- Natural Science Foundation of Guangdong Province (2017A030313459, 2017A030313840, 2018A0303130205)
- Key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangdong Higher Education Institutes, Sun Yat-sen University
- National Natural Science Foundation of China (81503052, 81771378, 81571244, 81971195)
- Topics
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- rifampicin, rotenone, microglial inflammation, Parkinson's disease, lysosomal function, autophagic flux, lysosomal acidification, autophagosome-lysosome fusion, JNK signaling, IL-1β, interleukin-6, chloroquine, autolysosomes
- MeSH terms
- Autophagosomes, Cell Survival, Cells, Cultured, Humans, Insecticides, Lysosomes, Microtubule-Associated Proteins, Rifampin, Rotenone, Microglia, Neuroprotective Agents, Vacuolar Proton-Translocating ATPases, RNA, Small Interfering
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