Neuroinflammatory and Amyloidogenic Activities of IL-32 beta in Alzheimer's Disease

Interleukin (IL)-32 beta can act as either pro-inflammatory or anti-inflammatory cytokines with being dependent on the status of disease development. Herein, we investigated whether IL-32 beta overexpression changes cytokine levels and affects amyloid-beta (A beta)-induced pro-inflammation in the brain. IL-32 beta transgenic (Tg) mice and non-Tg mice were intracerebroventricularly infused with A beta(1-42) once a day for 14 days, and then cognitive function was assessed by the Morris water maze test and passive avoidance test. Our data showed that IL-32 beta Tg mice increased memory impairment, glia activation, amyloidogenesis, and neuroinflammation. The expression of glial fibrillary acid protein (GFAP), Iba1, and beta-secretase 1 (BACE1) in the cortex and hippocampus was much higher in the A beta(1-42)-infused IL-32 beta Tg mice brain. The activation of signal transducer and activator of transcription 3 (STAT3) and nuclear factor-kappa B (NF-kappa B) was much higher in A beta(1-42)-infused IL-32 beta Tg mice brain. We also found that cytokines including IP-10, GM-CSF, JE, IL-13, and interferone-inducible T cell alpha chemoattractant (I-TAC) were elevated in A beta(1-42)-infused IL-32 beta Tg mice brain. These results suggest that IL-32 beta could activate NF-kappa B and STAT3, and thus affect neuroinflammation as well as amyloidogenesis, leading to worsening memory impairment.