Knockdown of TLR4 Represses the Paraquat-Induced Neuroinflammation and Microglial M1 Polarization
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ORIGINAL ARTICLE
Knockdown of TLR4 Represses the Paraquat-Induced Neuroinflammation and Microglial M1 Polarization Min Huang 1 & Yingying Li 1 & Tian Tian 1 & Kai Wang 1 & Yifan Wang 1 & Weiguang Yan 1 & Huifang Yang 1 Received: 4 June 2020 / Revised: 3 July 2020 / Accepted: 22 July 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Paraquat (PQ) is associated with multiple nervous system disorders including Parkinson’s disease. Despite the evidence that PQ could induce inflammatory responses in the central nervous system and largely contribute to neurotoxicity, the mechanisms of PQ-induced neuroinflammation are not yet fully understood. Toll-like receptor 4 (TLR4) could recognize various pathogens and initiate inflammation processes. Therefore, we investigated the role of TLR4 in PQ-induced neuroinflammation by using murine microglial immortalized BV-2 cell line. Normal microglia and TLR4-knockdown microglia were treated with PQ to evaluate signal transduction molecular expression, inflammatory responses, and microglial functions. Compared with normal microglia, PQ-induced production of pro-inflammatory cytokines was significantly reduced in TLR4-knockdown microglia. Levels of M1 markers were decreased, while levels of M2 markers were increased upon PQ exposure, confirming that TLR4 depletion inhibited the microglial M1 polarization. Besides, the migration and phagocytosis capability reduced by PQ were to some extent recovered in TLR4-knockdown microglia. Taken together, our results suggested that TLR4 mediated the neuroinflammatory responses in microglia and the depletion of TLR4 protects against PQ neurotoxicity. Keywords Paraquat . TLR4 . Neuroinflammatory responses . Microglia
Introduction Paraquat (1, 1′-dimethyl-4, 4′-bipyridinium, PQ), a widely used highly efficient and nonselective herbicide, has been demonstrated to be associated with multiple nervous system disorders such as Parkinson’s disease (Prasad et al. 2009; Lou et al. 2012). Neuroinflammation has been considered to be a crucial mediator in environmental neurotoxicant-induced progressive neural (Mitra et al. 2011; Costa et al. 2014). Microglia, the major resident immune cells in the central nervous system, plays as an active contributor to neuroinflammation (Rojo et al. 2014). Our previous study also revealed that PQ exposure could activate microglia into an inflammatory phenotype (Huang et al. 2019). However, the mechanisms of Min Huang and Yingying Li contributed equally to this work. * Huifang Yang [email protected] 1
The Department of Occupational and Environmental Health, School of Public Health and Management, Ningxia Medical University, 750004, 1160 Shengli Street, Xingqing District, Yinchuan 750004, China
PQ-induced neuroinflammation are not yet fully understood, and no effective therapeutic strategy has been found. Toll-like receptors (TLRs), a panel of type I transmembrane proteins, could recognize pathogen-associated molecular patterns (PAMPs), thereby initiating innate immune responses and in
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