Paraquat modulates microglia M1/M2 polarization via activation of TLR4-mediated NF-κB signaling pathway

Abstract

Paraquat (PQ) is a widely characterized neurotoxicant able to induce a series of nervous system disorders, including neurobehavioral defects and neurodegenerative diseases. Despite the direct evidence that PQ could induce inflammatory responses in central nervous system and largely contribute to neurotoxicity, the putative adverse effects of PQ on the neuroimmune interactions have rarely been investigated. Therefore, the present study investigated underlying mechanisms of PQ-induced inflammatory response in BV-2 microglia cells. Proliferation, migration and phagocytosis of BV-2 cells upon PQ exposure were first investigated to demonstrate that PQ did stimulate BV-2 microglia into an active phenotype. Increased microglia M1 markers expression and decreased microglia M2 markers expression confirmed that PQ induces BV-2 cells towards M1 activation. The levels of pro-inflammatory cytokines were determined using ELISA and western blotting assays, showing that paraquat significantly promote the secretion of pro-inflammatory mediators such as tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β) and interleukin 6 (IL-6). The up-regulation of TLR4/MyD88 protein expressions and enhanced translocation of NF-κB p65 protein upon PQ exposure were further demonstrated. Taken together, our results suggested that PQ induces M1 microglia polarization by increased production of pro-inflammatory molecules, which could be explained by the activation of the TLR4-mediated NF-κB signaling pathway.