Enhanced neuroinflammatory responses after systemic LPS injection in IL-32 beta transgenic mice

IL-32 is a proinflammatory cytokine, and involved in various diseases including infection, inflammation, and cancer. However, effects of IL-32 on neuroinflammation remain obscure. Herein, we examined the effects of IL-32 beta on systemic LPS-induced neuroinflammation using IL-32 beta transgenic (Tg) mice. IL-32 beta wild type (WT) and Tg mice received LPS injection (5 mg/kg, i.p.), and then neuroinflammatory responses were evaluated. Systemic LPS caused remarkable gliosis in the brain at 12 h regardless of genotypes. The gliosis in WT mice was sustained by 24 h, whereas it became more severe in Tg mice by 24 h. Proinflammatory cytokines and proteins were increased at 12 h both in WT and Tg brains. The elevated levels of TNF alpha and VCAM-1 were not altered over time, while levels of IL-6, IL-1 beta and iNOS were dropped in WT mice. In contrast, elevated levels IL-6, IL-1 beta, iNOS and VCAM-1 were sustained, and level of TNE alpha was augmented in Tg brains by 24 h. Interestingly, level of IL-10 mRNA in Tg mice was remarkably higher than in WT mice at 0 h, which was decreased at 12 h and maintained by 24 h. In WT brain, mRNA level of IL-10 was raised at 12 h after LPS injection, and further increased at 24 h. Activation of NF-kappa B signaling pathway was detected in glia cells after LPS injection which was exaggerated at 24 h in Tg mice in comparison to WT mice. These results indicate that IL-32 beta enhances neuroinflammatory responses caused by systemic LPS, and this might be attributable to prolonged activation of NE-kappa B signaling pathway.