title: The selective mGluR5 agonist CHPG attenuates SO2-induced oxidative stress and inflammation through TSG-6/NF-κB pathway in BV2 microglial cells.
abstract: Sulfur dioxide (SO2) is a common air pollutant and can cause harmful insults on neurons. Microglial activation has been implicated in the signaling cascades that contribute to neuronal cell death in various neurological disorders. In the present study, we found that SO2 derivatives decreased cell viability via inducing oxidative stress, inflammatory responses and apoptotic cell death in BV2 microglial cells. Pretreatment with (RS)-2-chloro-5-hydroxyphenylglycine (CHPG), an mGluR5 agonist, significantly attenuated the SO2-induced cytotoxicity, which was fully prevented by the mGluR5 antagonist MPEP. CHPG increased the expression of TNF-α stimulated gene/protein 6 (TSG-6), but decreased the activation of nuclear factor-κB (NF-κB) after SO2 derivatives treatment in BV2 cells. In addition, knockdown of TSG-6 expression by specific targeted short interfering RNA (siRNA) partially reversed the protection induced by CHPG. Therefore, our findings reveal a mechanistic basis for exploring the association between SO2 exposure and neurological disorders, and also for opening up therapeutic approaches of ameliorating neuronal injury resulting from exposure in atmospheric polluting environment.
authors.affiliation: Basic Medical Sciences Research Center, Shannxi Fourth People's Hospital, Xi'an, Shannxi 710043, China.
authors.forename: Jun-Ling
authors.initials: JL
authors.lastname: Qiu
authors.affiliation: Department of Neurology, Shannxi Fourth People's Hospital, Xi'an, Shannxi 710043, China.
authors.forename: Wen-Li
authors.initials: WL
authors.lastname: Zhu
authors.affiliation: Basic Medical Sciences Research Center, Shannxi Fourth People's Hospital, Xi'an, Shannxi 710043, China.
authors.forename: Yu-Jie
authors.initials: YJ
authors.lastname: Lu
authors.affiliation: Basic Medical Sciences Research Center, Shannxi Fourth People's Hospital, Xi'an, Shannxi 710043, China.
authors.forename: Zheng-Fa
authors.initials: ZF
authors.lastname: Bai
authors.affiliation: Department of Neurosurgery, Shannxi Fourth People's Hospital, Xi'an, Shannxi 710043, China.
authors.forename: Zhi-Gang
authors.initials: ZG
authors.lastname: Liu
authors.affiliation: Department of Neurology, Shannxi Fourth People's Hospital, Xi'an, Shannxi 710043, China.
authors.forename: Pei
authors.initials: P
authors.lastname: Zhao
authors.affiliation: Basic Medical Sciences Research Center, Shannxi Fourth People's Hospital, Xi'an, Shannxi 710043, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Sun
authors.affiliation: Basic Medical Sciences Research Center, Shannxi Fourth People's Hospital, Xi'an, Shannxi 710043, China.
authors.forename: Ya-Bin
authors.initials: YB
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Shannxi Fourth People's Hospital, Xi'an, Shannxi 710043, China. Electronic address: lihua_sx4y@126.com.
authors.forename: Hua
authors.initials: H
authors.lastname: Li
authors.affiliation: Basic Medical Sciences Research Center, Shannxi Fourth People's Hospital, Xi'an, Shannxi 710043, China. Electronic address: liuwei_sx4y@126.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
mesh_terms: D000818:Animals; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology; D018836:Inflammation Mediators / Q000378:metabolism; D051379:Mice; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010648:Phenylacetates / Q000494:pharmacology*; D064529:Receptor, Metabotropic Glutamate 5 / Q000819:agonists*; D013458:Sulfur Dioxide / Q000633:toxicity
chemical_list: C107349:2-chloro-5-hydroxyphenylglycine; D016207:Cytokines; C578936:Grm5 protein, mouse; D018836:Inflammation Mediators; D010648:Phenylacetates; D064529:Receptor, Metabotropic Glutamate 5; D013458:Sulfur Dioxide; D005998:Glycine
keywords: Inflammation; Microglia; NF-κB; SO(2); TSG-6; mGluR5