Knockdown of TLR4 Represses the Paraquat-Induced Neuroinflammation and Microglial M1 Polarization
| Autor: | Min Huang, Yingying Li, Yifan Wang, Huifang Yang, Kai Wang, Tian Tian, Weiguang Yan |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Paraquat Phagocytosis Central nervous system Inflammation Toxicology 03 medical and health sciences Mice 0302 clinical medicine medicine Animals Neuroinflammation Microglia Chemistry General Neuroscience Neurotoxicity Parkinson Disease medicine.disease Cell biology Toll-Like Receptor 4 030104 developmental biology medicine.anatomical_structure Gene Knockdown Techniques TLR4 Cytokines medicine.symptom Signal transduction Nervous System Diseases 030217 neurology & neurosurgery Signal Transduction Transcription Factors |
| Zdroj: | Neurotoxicity research. 38(3) |
| ISSN: | 1476-3524 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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