TY - JOUR
T1 - Involvement of oncogenic protein β-catenin in LPS-induced cytotoxicity in mouse mononuclear leukemia RAW 264.7 cells
AU - Koide, Naoki
AU - Naiki, Yoshikazu
AU - Odkhuu, Erdenezaya
AU - Tsolmongyn, Bilegtsaikhan
AU - Komatsu, Takayuki
AU - Ito, Kiyoaki
AU - Yoshida, Tomoaki
AU - Yokochi, Takashi
PY - 2013
Y1 - 2013
N2 - 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.
AB - 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.
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U2 - 10.3727/096504013X13793555706803
DO - 10.3727/096504013X13793555706803
M3 - Article
C2 - 24330853
AN - SCOPUS:84890941275
SN - 0965-0407
VL - 21
SP - 59
EP - 65
JO - Oncology Research
JF - Oncology Research
IS - 1
ER -