Abstract
Objective: Indoleamine 2,3-dioxygenase (IDO) activity plays an important role in many neurological disorders in the central nervous system, which may be associated with immunomodulation or anti-inflammatory activity. However, the action of IDO in the ischemic condition is still poorly understood. The purpose of the present study is to explore the expression and action of IDO in stem cell culture under oxygen and glucose deprivation.Methods: Neural progenitor cells were obtained from the human embryonic stem cell line BG01. These cells underwent oxygen and glucose deprivation. We examined the IDO expression at 3 and 8 h of oxygen and glucose deprivation and then examined neuronal progenitor cell viability in the normal and oxygen and glucose deprivation condition using the [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. In addition, we studied the effect of IDO inhibition and the expression of TNF-α, IGF-1, VEGF, IL-6, FGFβ, TGFβ, EGF, and Leptin to explore the mechanism of IDO under the oxygen and glucose deprivation.Results: IDO expression in neural progenitor cells increased under oxygen and glucose deprivation, which is closely associated with cell death (p < 0.05). Inhibiting IDO did not affect cell survival in normal neural progenitor cells. However, inhibiting IDO could attenuate cell viability under oxygen and glucose deprivation (p < 0.05). Further study demonstrated that IDO expression was closely associated to the growth factor’s leptin expression.Conclusions: Our results demonstrated that an increase of IDO under oxygen and glucose deprivation was associated with cell death, suggesting that inhibiting IDO could be a target for neuroprotection.
Highlights
Ischemic stroke is one of the leading causes of death and adult disability worldwide, which leads to massive cell death and complex pathological changes (Tang et al, 2016; Naghavi et al, 2017; Wang et al, 2017)
A recent study in a mouse model of middle cerebral artery occlusion demonstrated that the macrophages/microglia could enhance indoleamine 2,3-dioxygenase 1 (IDO1)-dependent neurotoxic kynurenine metabolism during ischemic pathogenesis, which was closely related to the post-stroke depression (Koo et al, 2018)
Western blot results showed that IDO expression was significantly increased in Neural stem/progenitor cells (NPCs) after 3 and 8 h of Oxygen-Glucose Deprivation (OGD) compared to the NPCs that were in a normal condition (Figure 2, p < 0.05)
Summary
Ischemic stroke is one of the leading causes of death and adult disability worldwide, which leads to massive cell death and complex pathological changes (Tang et al, 2016; Naghavi et al, 2017; Wang et al, 2017). Our previous studies demonstrated that during an ischemic stroke attack, resident microglia/macrophages were activated, which could increase cytokines such as IL1β, IL-6, TNFα, chemokines CXC, CC, CX3C, and XC, and adhesion molecules, calcium-independent integrins, and calcium-dependent cadherins expression in the ischemic region as well as system blood circulation (Ma et al, 2017). Activated macrophages/microglia triggered the immune system cascade through activating regulatory T cells, T cells, B cells, and the complement system (Wang et al, 2015). A recent study in a mouse model of middle cerebral artery occlusion demonstrated that the macrophages/microglia could enhance indoleamine 2,3-dioxygenase 1 (IDO1)-dependent neurotoxic kynurenine metabolism during ischemic pathogenesis, which was closely related to the post-stroke depression (Koo et al, 2018). The role of IDO in the cell death under oxygen and glucose deprivation is largely unknown
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