GSK-3β inhibition attenuates LPS-induced death but aggravates radiation-induced death via down-regulation of IL-6.

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.