GSK-3β Inhibition Attenuates LPS-Induced Death but Aggravates Radiation-Induced Death via Down-Regulation of IL-6

Cellular Physiology and Biochemistry

关键词: Glycogen synthase kinase-3;    LPS;    Radiation;    IL-6;   

DOI  :  10.1159/000356606

学科分类：分子生物学，细胞生物学和基因

来源: S Karger AG

【 摘 要 】

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.

【 授权许可】

CC BY-NC-ND