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Factors ameliorate pro-inflammatory microglia polarization through inhibition of reactive astrocytes induced by 2-chloroethanol
- Source :
- Ecotoxicology and Environmental Safety, Vol 261, Iss , Pp 115130- (2023)
- Publication Year :
- 2023
- Publisher :
- Elsevier, 2023.
-
Abstract
- 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.
Details
- Language :
- English
- ISSN :
- 01476513
- Volume :
- 261
- Issue :
- 115130-
- Database :
- Directory of Open Access Journals
- Journal :
- Ecotoxicology and Environmental Safety
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.76a4db3d47414c5c80e30a5f4e4e76b9
- Document Type :
- article
- Full Text :
- https://doi.org/10.1016/j.ecoenv.2023.115130