关键词: 神经炎性反应, 坏死性凋亡, 小胶质细胞, 脂多糖, 塞妥昔单抗

Abstract: Objective To explore the regulatory mechanism of microglia apoptosis in neuroinflammation. Methods LPS was used to establish mouse microglia cell line BV2 cells as a neuroinflammatory microglia model, IL-6 antagonist siltuximab was applied to treat LPS-induced BV2 cells. CCK-8 was used to detect the proliferation of cells. Cell apoptosis was detected by flow cytometry. ELISA kit was used to detect the content of pro-inflammatory related factors IL-6 and TNF-α. The expression of M1 polarization markers IL-1β, IFN-γ and M2 polarization markers CD206, Arg-1 in BV2 cell was detected by qRT-PCR. The expression of JAK-STAT3 signaling pathway key proteins and necroptosis related proteins RIP1 and RIP3 was detected by Western blot. Results After LPS induction, the proliferation of BV2 cells decreased, apoptosis increased, and the contents of inflammatory factors IL-6 and TNF-α increased (P＜0.01). The expression of M1 polarization markers IL-1β and IFN-γ increased, and the expression of M2 polarization markers CD206 and Arg-1 decreased(P＜0.01). The phosphorylation of JAK-STAT3 key protein increased, and the relative protein expression of RIP1 and RIP3 (P＜0.01). After treatment with IL-6 antagonist siltuximab, phosphorylation of JAK-STAT3 key proteins decreased, and RIP1 and RIP3 protein decreased (P＜0.01). Conclusions IL-6 may activate JAK-STAT3 signaling pathway to promote necroptosis of mouse microglia in neuroinflammation.

Key words: neuroinflammation, necroptosis, microglia, lipopolysaccharide, siltuximab