小胶质细胞
细胞因子
星形胶质细胞
诱导多能干细胞
神经炎症
创伤性脑损伤
背景(考古学)
神经科学
趋化因子
免疫学
肿瘤坏死因子α
生物
促炎细胞因子
炎症
细胞生物学
医学
中枢神经系统
胚胎干细胞
生物化学
古生物学
精神科
基因
作者
Aftab Alam,Tanya Singh,Saeed Kayhanian,Jonathan Tjerkaski,Núria Marcó García,Keri L.H. Carpenter,Rickie Patani,Caroline Lindblad,Eric Peter Thelin,Yasir Ahmed Syed,Adel Helmy
标识
DOI:10.1089/neu.2022.0508
摘要
The neuroinflammatory response after traumatic brain injury (TBI) is implicated as a key mediator of secondary injury in both the acute and chronic periods after primary injury. Microglia are the key innate immune cell in the central nervous system, responding to injury with the release of cytokines and chemokines. In this context, we aimed to characterize the downstream cytokine response of human induced pluripotent stem cell (iPSC)-derived microglia when stimulated with five separate cytokines identified after human TBI. The iPSC-derived microglia were exposed to interleukin (IL)-1β, IL-4, IL-6, IL-10, and tumor necrosis factor (TNF) in the concentration ranges identified in clinical TBI studies. The downstream cytokine response was measured against a panel of 37 separate cytokines over a 72h time-course. The secretome revealed concentration-, time- and combined concentration and time-dependent downstream responses. TNF appeared to be the strongest inducer of downstream cytokine changes (51), followed by IL-1β (26) and IL-4 (19). IL-10 (11) and IL-6 (10) produced fewer responses. We also compare these responses with our previous studies of iPSC-derived neuronal and astrocyte cultures and the in vivo human TBI cytokine response. Notably, we found microglial culture to induce both a wider range of downstream cytokine responses and a greater fold change in concentration for those downstream responses, compared with astrocyte and neuronal cultures. In summary, we present a dataset for human microglial cytokine responses specific to the secretome found in the clinical context of TBI. This reductionist approach complements our previous datasets for astrocyte and neuronal responses and will provide a platform to enable future studies to unravel the complex neuroinflammatory network activated after TBI.
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