Uric acid inhibits HMGB1-TLR4-NF- κB signaling to alleviate oxygen-glucose deprivation/reoxygenation injury of microglia.

Uric acid inhibits HMGB1-TLR4-NF-κB signaling to alleviate oxygen-glucose deprivation/reoxygenation injury of microglia. Biochem Biophys Res Commun. 2021 Jan 08;540:22-28 Authors: Wang Q, Zhao H, Gao Y, Lu J, Xie, Yu W, He F, Liu W, Hisatome I, Yamamoto T, Wang W, Cheng J Abstract Mounting evidence has implicated inflammation in ischemia-reperfusion injury following acute ischemic stroke (AIS). Microglia remain the primary initiator and participant of brain inflammation. Emerging evidence has indicated that uric acid has promise for the treatment of AIS, but its explicit mechanisms remain elusive. Here, we observed that uric acid reduced the severity of cerebral infarction and attenuated the activation of microglia in the cerebral cortex in a mouse middle cerebral-artery occlusion/reperfusion model. Thus, we speculated that uric acid may play a role by directly interfering with the inflammatory response of microglia. First, we investigated whether the HMGB1-TLR4-NF-κB signaling plays a role in oxygen glucose deprivation and reperfusion (OGD/R) injury of BV2 cells. Inhibition of the signaling significantly reduced the release of the proinflammatory cytokines tumor necrosis factor α (TNF-α), interleukin 1β (IL1β), and IL6 caused by OGD/R in BV2 cells. Second, uric acid weakened the decreased cell viability and lactate dehydrogenase release induced by OGD/R in BV2 cells. Finally, uric acid reduced the release of the proinflammator...
Source: Biochemical and Biophysical Research communications - Category: Biochemistry Authors: Tags: Biochem Biophys Res Commun Source Type: research