title: Nicorandil inhibits inflammasome activation and Toll-like receptor-4 signal transduction to protect against oxygen-glucose deprivation-induced inflammation in BV-2 cells.
abstract: OBJECTIVE
  Our previous studies have demonstrated adenosine triphosphate-sensitive potassium channel (KATP channel) openers could protect against inflammatory response in brain disease, but little is known about the mechanisms involved in KATP channel openers inhibiting neuroinflammation.
  
  
  RESULTS
  In the present study, we found that oxygen-glucose deprivation (OGD) resulted in BV-2 cells activation, significantly increased tumor necrosis factor-alpha and interleukin-1beta (IL-1β) levels, accompanied by downregulating Kir6.1 subunit. Pretreatment with nicorandil, a KATP channel opener, could attenuate OGD-induced BV-2 cells activation and inhibit pro-inflammatory factors release. Further study demonstrated that OGD activated Toll-like receptor-4 (TLR4) signaling pathway and NOD-like receptor pyrin domain containing three inflammasome, thereby increased IL-1β production. Pretreatment with nicorandil could reverse the two pathways involved in IL-1β production.
  
  
  CONCLUSIONS
  Our findings reveal that KATP channel openers could protect against OGD-induced neuroinflammation via inhibiting inflammasome activation and TLR4 signal transduction.
authors.affiliation: Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, Nanjing Medical University, Nanjing, China.
authors.forename: An-Peng
authors.initials: AP
authors.lastname: Zhao
authors.forename: Yin-Feng
authors.initials: YF
authors.lastname: Dong
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Jun
authors.initials: J
authors.lastname: Gu
authors.forename: Xiu-Lan
authors.initials: XL
authors.lastname: Sun
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D020170:Caspase 1 / Q000378:metabolism; D002461:Cell Line, Transformed; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation / Q000187:drug effects*; D005947:Glucose / Q000172:deficiency; D000860:Hypoxia / Q000150:complications; D051550:I-kappa B Kinase / Q000378:metabolism; D007249:Inflammation / Q000209:etiology / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism; D054086:KATP Channels / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D051379:Mice; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D020108:Nicorandil / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects*; D051193:Toll-Like Receptors / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014803:Vitamin B Complex / Q000494:pharmacology*
chemical_list: D002352:Carrier Proteins; D053583:Interleukin-1beta; D054086:KATP Channels; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; C092520:uK-ATP-1 potassium channel; D014803:Vitamin B Complex; D020108:Nicorandil; D007770:L-Lactate Dehydrogenase; D051550:I-kappa B Kinase; D020170:Caspase 1; D005947:Glucose
keywords: ATP-sensitive potassium channel; Inflammasome; Neuroinflammation; Nicorandil; Oxygen-glucose deprivation