TP1-4 In vitro induced cytokine response of astrocytes modelling conditions in human traumatic brain injury

Autor: Claire E. Hall, Tamara Tajsic, Klh Carpenter, Adel Helmy, Arvid Frostell, Rickie Patani, Pja Hutchinson, Eric Peter Thelin
Rok vydání: 2019
Předmět:
Zdroj: Journal of Neurology, Neurosurgery & Psychiatry. 90:e11.1-e11
ISSN: 1468-330X
0022-3050
DOI: 10.1136/jnnp-2019-abn.34
Popis: ObjectivesThe objective of this study was to investigate how in vitro astrocyte cultures respond to cytokine pro- and anti-inflammatory cytokine concentrations, corresponding to those seen in the aftermath of human TBI, by analysing downstream cytokine generation.DesignIn vitro study.SubjectsHuman induced pluripotent stem cells (iPSC)-derived astrocytes.MethodsThe astrocytes were exposed to levels of TNF (1–10,000 pg/ml), IL-6 (100–1,000,000 pg/ml), Interleukin-1β (IL-1β, 1–10,000 pg/ml), Interleukin-4 (IL-4, 1–10,000 pg/ml) and Interleukin-10 (IL-10, 1–10,000 pg/ml). Following 24, 48 and 72 hours, culture supernatant was extracted and analysed using a human cytokine/chemokine 39-plex luminex assay (ThermoFisher).ResultsThe astrocyte secretome revealed concentration-, time- or concentration*time-dependent production of downstream cytokines (12, 8 and 2 cytokines, respectively pConclusionsiPSC-derived astrocytes exposed to cytokine concentrations reflecting those in TBI generate an increased downstream cytokine production, especially when exposed to IL-1β and TNF. This is in contrast to our previous work on neuronal cultures where IL-1β only produced a few down-stream cytokines.1 More work is needed to better understand how different cells in the CNS respond to the neuroinflammatory milieu after TBI alone and in combination.
Databáze: OpenAIRE