Abstract
Propofol is an established anesthetic widely used for induction and maintenance of anesthesia. We investigated propofol for its anti-inflammatory effects on microglia and found that propofol treatment is associated with substantial lower levels of extracellular vesicles (EVs) in immune activated microglia. Importantly, EVs collected from immune activated microglia reversed propofol-mediated anti-inflammatory and neuroprotective effects, suggesting that propofol reduces proinflammatory microglia activation and microglia-mediated neurotoxicity through inhibition of EV release. These data shed new insight into a novel molecular mechanism of propofol-mediated neuroprotective and immunomodulatory effects through inhibition of EV release.
| Original language | French |
|---|---|
| Article number | 476962 |
| Journal | Journal of Neuroimmunology |
| Volume | 333 |
| DOIs | |
| State | Published - Aug 15 2019 |
Keywords
- Anesthetics
- Extracellular vesicles
- Microglia
- Neuroinflammation
- Neurotoxicity
- Propofol
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
- Neurology
- Clinical Neurology
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Propofol reduces microglia activation and neurotoxicity through inhibition of extracellular vesicle release. / Liu, Jianhui; Li, Yuju; Xia, Xiaohuan; Yang, Xiaoyu; Zhao, Runze; Peer, Justin; Wang, Hongyun; Tong, Zenghan; Gao, Fengtong; Lin, Hai; Wu, Beiqing; Huang, Yunlong; Zheng, Jialin C.
In: Journal of Neuroimmunology, Vol. 333, 476962, 15.08.2019.Research output: Contribution to journal › Article › peer-review
}
TY - JOUR
T1 - Propofol reduces microglia activation and neurotoxicity through inhibition of extracellular vesicle release
AU - Liu, Jianhui
AU - Li, Yuju
AU - Xia, Xiaohuan
AU - Yang, Xiaoyu
AU - Zhao, Runze
AU - Peer, Justin
AU - Wang, Hongyun
AU - Tong, Zenghan
AU - Gao, Fengtong
AU - Lin, Hai
AU - Wu, Beiqing
AU - Huang, Yunlong
AU - Zheng, Jialin C.
N1 - Funding Information: We kindly thank Dr. Zeljka Korade for providing the N2A cell line and for technical support. This work was supported by grants from National Key Basic Research Program of China (973Program Grant No. 2014CB965001 to JZ), State Key Program of the National Natural Science Foundation of China (# 81830037 to JZ), Joint Research Fund for Overseas Chinese, Hong Kong and Macao Young Scientists of the National Natural Science Foundation of China (# 81329002 to JZ), National Natural Science Foundation of China (# 81600934 to JH), Natural Science Foundation of Shanghai , China (# 16ZR1432200 to JH), and National Institutes of Health : 1R01NS097195-01 (JZ). Funding Information: We kindly thank Dr. Zeljka Korade for providing the N2A cell line and for technical support. This work was supported by grants from National Key Basic Research Program of China (973Program Grant No. 2014CB965001 to JZ), State Key Program of the National Natural Science Foundation of China (#81830037 to JZ), Joint Research Fund for Overseas Chinese, Hong Kong and Macao Young Scientists of the National Natural Science Foundation of China (#81329002 to JZ), National Natural Science Foundation of China (#81600934 to JH), Natural Science Foundation of Shanghai, China (#16ZR1432200 to JH), and National Institutes of Health: 1R01NS097195-01 (JZ). Funding Information: Our results on the in vitro anti-neuroinflammation and neuroprotective effect of propofol are similar to those of Zheng et al. and Gui et al., who recently demonstrated the neuroprotective effect of propofol ( Gui et al., 2012 ; Zheng et al., 2018 ). These prior studies identified miR-155, Toll-like receptor 4, and glycogen synthase kinase-3β as the key mechanisms for the neuroprotective effect of propofol. Although these mechanisms may play a significant role in anti-inflammatory responses and neuroprotection, our data showed that propofol significantly inhibits EV release from LPS-activated microglia. EVs are a heterogeneous group of membrane vesicles of endosomal and plasma membrane origin that are important mediators of cell-to-cell communication. EVs contain proteins, lipids, and microRNAs that can mediate various signaling functions ( Mathivanan et al., 2010 ). EV release can be modulated by reactive oxygen species ( Blanc et al., 2007 ), inflammation ( Bianco et al., 2005 ), and by ATP ( Savina et al., 2003 ). Our previous work found that immune activation induced by LPS or TNF-α can increase EV release from microglia and astrocytes, ( Wang et al., 2017 ; Wu et al., 2015 ; Wu et al., 2018 ). In the current study, we used LPS as the inflammation-inducing agent for the microglia. Importantly, propofol markedly decreased LPS-mediated EV release in microglia, which was documented and supported by both NTA and by Western blotting analysis of EV markers. Addition of EVs can partially reverse propofol-mediated anti-neuroinflammation and neuroprotective effects in microglia, suggesting that propofol decreases microglia activation and exerts neuroprotection, at least in part, by downregulating EV release. Publisher Copyright: © 2019 The Authors
PY - 2019/8/15
Y1 - 2019/8/15
N2 - Propofol is an established anesthetic widely used for induction and maintenance of anesthesia. We investigated propofol for its anti-inflammatory effects on microglia and found that propofol treatment is associated with substantial lower levels of extracellular vesicles (EVs) in immune activated microglia. Importantly, EVs collected from immune activated microglia reversed propofol-mediated anti-inflammatory and neuroprotective effects, suggesting that propofol reduces proinflammatory microglia activation and microglia-mediated neurotoxicity through inhibition of EV release. These data shed new insight into a novel molecular mechanism of propofol-mediated neuroprotective and immunomodulatory effects through inhibition of EV release.
AB - Propofol is an established anesthetic widely used for induction and maintenance of anesthesia. We investigated propofol for its anti-inflammatory effects on microglia and found that propofol treatment is associated with substantial lower levels of extracellular vesicles (EVs) in immune activated microglia. Importantly, EVs collected from immune activated microglia reversed propofol-mediated anti-inflammatory and neuroprotective effects, suggesting that propofol reduces proinflammatory microglia activation and microglia-mediated neurotoxicity through inhibition of EV release. These data shed new insight into a novel molecular mechanism of propofol-mediated neuroprotective and immunomodulatory effects through inhibition of EV release.
KW - Anesthetics
KW - Extracellular vesicles
KW - Microglia
KW - Neuroinflammation
KW - Neurotoxicity
KW - Propofol
UR - http://www.scopus.com/inward/record.url?scp=85065733881&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85065733881&partnerID=8YFLogxK
U2 - 10.1016/j.jneuroim.2019.05.003
DO - 10.1016/j.jneuroim.2019.05.003
M3 - Article
C2 - 31108401
AN - SCOPUS:85065733881
VL - 333
JO - Advances in Neuroimmunology
JF - Advances in Neuroimmunology
SN - 0165-5728
M1 - 476962
ER -