The selective mGluR5 agonist CHPG attenuates SO2-induced oxidative stress and inflammation through TSG-6/NF-κB pathway in BV2 microglial cells

• SO2 derivatives induce oxidative stress and inflammation in BV2 cells.
• CHPG reduces SO2 derivatives-induced cytotoxicity in BV2 cells.
• CHPG-induced effects on SO2-induced cytotoxicity are prevented by MPEP.
• CHPG attenuates SO2 derivatives-induced oxidative stress and inflammation.
• CHPG-induced protection is partly dependent on TSG-6/NF-κB pathway.

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.