Factors ameliorate pro-inflammatory microglia polarization through inhibition of reactive astrocytes induced by...

Our previous studies have demonstrated that the crosstalk between astrocytes and microglia may trigger and amplify the neuroinflammatory response and, in turn, cause brain edema in 1,2-dichloroethane (1,2-DCE)-intoxicated mice. Moreover, findings from our in vitro studies showed that astrocytes are more sensitive to 2-chloroethanol (2-CE), an intermediate metabolite of 1,2-DCE, than microglia, and 2-CE-induced reactive astrocytes (RAs) can promote microglia polarization through releasing the pro-inflammatory mediators. Therefore, it is essential to explore therapeutic agents that may ameliorate microglia polarization through inhibition of 2-CE-induced RAs, which remains unclear till now. Results of this study revealed that exposure to 2-CE could induce RAs with pro-inflammatory effects, and fluorocitrate (FC), GIBH-130 (GI) and diacerein (Dia) pretreatment could all abolish the pro-inflammatory effects of 2-CE-induced RAs. FC and GI pretreatment might suppress 2-CE-induced RAs through inhibition of p38 mitogen-activated protein kinase (p38 MAPK)/activator protein-1 (AP-1) and nuclear factor-kappaB (NF-κB) signaling pathways, but Dia pretreatment might only inhibit p38 MAPK/NF-κB signaling pathway. FC, GI, and Dia pretreatment could all suppress the pro-inflammatory microglia polarization through inhibition of 2-CE-induced RAs. Meanwhile, GI and Dia pretreatment could also restored the anti-inflammatory microglia polarization via inhibition of 2-CE-induced RAs. However, FC pretreatment could not affect the anti-inflammatory polarization of microglia through inhibition of 2-CE-induced RAs. Taken together, findings from the present study demonstrated that FC, GI, and Dia might be the potential candidates with different characteristic for therapeutic use in 1,2-DCE poisoning.