Article ; Online: Modeling the Inflammatory Response of Traumatic Brain Injury Using Human Induced Pluripotent Stem Cell Derived Microglia.
2023 Volume 40, Issue 19-20, Page(s) 2164–2173
Abstract: 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, ... ...
Abstract | 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 |
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MeSH term(s) | Animals ; Humans ; Microglia/pathology ; Interleukin-10 ; Induced Pluripotent Stem Cells ; Interleukin-6 ; Interleukin-4 ; Disease Models, Animal ; Brain Injuries, Traumatic/complications ; Cytokines ; Brain Injuries/complications ; Tumor Necrosis Factor-alpha |
Chemical Substances | Interleukin-10 (130068-27-8) ; Interleukin-6 ; Interleukin-4 (207137-56-2) ; Cytokines ; Tumor Necrosis Factor-alpha |
Language | English |
Publishing date | 2023-07-25 |
Publishing country | United States |
Document type | Journal Article ; Research Support, Non-U.S. Gov't |
ZDB-ID | 645092-1 |
ISSN | 1557-9042 ; 0897-7151 |
ISSN (online) | 1557-9042 |
ISSN | 0897-7151 |
DOI | 10.1089/neu.2022.0508 |
Database | MEDical Literature Analysis and Retrieval System OnLINE |
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