title: GSK-3β inhibition attenuates LPS-induced death but aggravates radiation-induced death via down-regulation of IL-6.
abstract: BACKGROUND
  Exposure of high dose ionizing radiation is lethal. Signal pathways involved in radiation biology reaction still remain illdefined. Lipopolysaccharides (LPS), the ligands of Toll-like receptor 4(TLR4), could elicit strong immune responses. Glycogen synthase kinase-3β(GSK-3β) promotes the production of inflammatory molecules and cell migration. Inhibition of GSK-3β provides protection against inflammation in animal models. The aim of the study was to investigate role of GSK-3β in LPS shock and ionizing radiation.
  
  
  METHODS
  WT or IL-6(-/-)mice or cells were pretreated with SB216763, a GSK-3β inhibitor, and survival of the mice was determined. Cell viability was assayed by Cell Counting Kit. Apoptosis was assayed by Annexin V-PI double staining. Serum concentrations of IL-6 and TNF-α were determined by ELISA.
  
  
  RESULTS
  SB216763 attenuated LPS induced mice or cell death but aggravated radiation induced mice or cell death. SB216763 reduced IL-6, but not TNF-α levels in vivo. IL-6(-/-) mice were more resistant to LPS-induced death but less resistant to radiation-induced death than wild type mice.
  
  
  CONCLUSIONS
  Inhibition of GSK-3β conferred resistance to LPS shock but fostered death induced by ionizing radiation. Inhibition of GSK-3β was effective by reducing IL-6.
authors.affiliation: Department of Radiation Medicine, Faculty of Naval Medicine, Second Military Medical University, Xiangyin Road, Shanghai, PR China.
authors.forename: Bailong
authors.initials: B
authors.lastname: Li
authors.forename: Chaoxiong
authors.initials: C
authors.lastname: Zhang
authors.forename: Feng
authors.initials: F
authors.lastname: He
authors.forename: Wen
authors.initials: W
authors.lastname: Liu
authors.forename: Yanyong
authors.initials: Y
authors.lastname: Yang
authors.forename: Hu
authors.initials: H
authors.lastname: Liu
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.forename: Jie
authors.initials: J
authors.lastname: Wang
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.forename: Bo
authors.initials: B
authors.lastname: Deng
authors.forename: Fu
authors.initials: F
authors.lastname: Gao
authors.forename: Jianguo
authors.initials: J
authors.lastname: Cui
authors.forename: Cong
authors.initials: C
authors.lastname: Liu
authors.forename: Jianming
authors.initials: J
authors.lastname: Cai
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D015536:Down-Regulation / Q000187:drug effects / Q000528:radiation effects; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D007211:Indoles / Q000494:pharmacology; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000633:toxicity; D008301:Maleimides / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011839:Radiation, Ionizing; D015398:Signal Transduction / Q000187:drug effects / Q000528:radiation effects; D015996:Survival Rate; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D007211:Indoles; D015850:Interleukin-6; D008070:Lipopolysaccharides; D008301:Maleimides; C417521:SB 216763; D014409:Tumor Necrosis Factor-alpha; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D038362:Glycogen Synthase Kinase 3