Study On The Effect And Mechanism Of IL-17 In Alzheimer’s Disease

【Objective】 There is a growing emphasis on the role of immune and inflammatory mechanisms in the progression of Alzheimer’s disease(AD), previous studies have demonstrated that inflammation response are widely involved in the pathological process of AD. IL-17 was reported to be involved in the immune inflammation response of AD and a variety of other neurological disorders. However, the specific mechanism of action is unclear. In the present study, we performed a cell experiments to investigate the effect and mechanism of IL-17 in AD.【Methods】 U251 and SH-SY5 Y cells were cultured in vitro with an appropriate concentration of Aβ1-42. The effect of IL-17 on both cell viability, IL-1β expression levels, NF-κB activation and caspase-3 expression levels were detected by using the method of MTT, RT-PCR, Western blot etc. All the data were statistically analyzed using SPSS 20.0.【Results】 1. The expression of IL-1β at RNA and protein levels in U251 cell were significantly increased(P<0.05) after treated with IL-17 for 6h. Blocking the IL-17 receptor can significantly inhibit the expression of IL-1β(P<0.05). 2. NF-κB activation was detected both in the two cell lines after treated with IL-17 at the time point 3h and 6h(P<0.05). Blocking the IL-17 receptor can significantly inhibit NF-κB activation(P <0.05). 3. The expression of caspase-3 was detected at the time point 6h, as well as the decrease of cell viability(P <0.05). Blocking the IL-17 receptor can significantly inhibit the expression of caspase-3, and the decrease the cell viability.【Conclusions】 1. IL-17 involved in the inflammation response of AD, and plays an important role in the progression of AD. 2. Activation of glial cells by IL-17 in the early stage of AD inflammation response has a neuroprotective effect. In the late stage of AD inflammation, persistent activation of glial cells, and IL-17 induced neuronal and glialapoptosis, which possibly due to the expression of caspase-3 induced by IL-17, increase the pathological lesions of AD. 3. IL-17 activates glial cells and caspase-3 expression possibly through the NF-κB signaling pathway. 4. Regulate the key factors of IL-17 signaling pathway(receptor, NF-κB, etc.) may become a new promising target for treatment of AD.