title: Involvement of oncogenic protein β-catenin in LPS-induced cytotoxicity in mouse mononuclear leukemia RAW 264.7 cells.
abstract: A toll-like receptor 4 (TLR-4) ligand, lipopolysaccharide (LPS) not only activates expression and secretion of inflammatory cytokines, but it also often shows toxicity in monocytes. Whether an oncogenic protein, β-catenin, is positively involved in LPS-induced cytotoxicity in a mouse leukemic monocyte cell line, RAW 264.7, was examined. TWS119, a GSK-3β inhibitor, increased LPS-induced β-catenin accumulation in the nucleus and augmented LPS-induced cytotoxicity. Cardamonin, a β-catenin inhibitor, inhibited LPS-induced β-catenin accumulation in the nucleus and reduced LPS-induced cytotoxicity. To confirm that β-catenin is involved in LPS-induced cytotoxicity, silencing of β-catenin expression by siRNA was carried out. The results were that knockdown of β-catenin reduced LPS-induced cytotoxicity. Interestingly, Cardamonin treatment or β-catenin silencing reduced LPS-induced endoplasmic reticulum (ER) stress responses such as PERK and e1F-2α phosphorylation and CHOP expression. Moreover, TWS119 increased LPS-induced ER stress responses. On the basis of these results, the oncogenic protein β-catenin is considered to be positively involved in LPS-induced cytotoxicity, possibly by downregulating ER stress responses.
authors: Department of Microbiology and Immunology, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan.
authors: Naoki
authors: N
authors: Koide
authors: Yoshikazu
authors: Y
authors: Naiki
authors: Erdenezaya
authors: E
authors: Odkhuu
authors: Bilegtsaikhan
authors: B
authors: Tsolmongyn
authors: Takayuki
authors: T
authors: Komatsu
authors: Kiyoaki
authors: K
authors: Ito
authors: Tomoaki
authors: T
authors: Yoshida
authors: Takashi
authors: T
authors: Yokochi
mesh_terms: D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D047188:Chalcones / Q000494:pharmacology; D004347:Drug Interactions; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects / Q000502:physiology; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D007938:Leukemia; D008070:Lipopolysaccharides / Q000633:toxicity*; D051379:Mice; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism*; D010766:Phosphorylation; D011743:Pyrimidines / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D051176:beta Catenin / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*
chemical_list: C495267:CTNNB1 protein, mouse; D047188:Chalcones; D008070:Lipopolysaccharides; D011743:Pyrimidines; D011758:Pyrroles; D034741:RNA, Small Interfering; C547688:TWS 119; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D051176:beta Catenin; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D038362:Glycogen Synthase Kinase 3; C436747:cardamonin