Macrophage migration inhibitory factor activates inflammatory responses of astrocytes through interaction with CD74 receptor

Su, Yu; Wang, Yingjie; Zhou, Yue; Zhu, Zhenjie; Zhang, Qing; Zhang, Xuejie; Wang, Wenjuan; Gu, Xiaosong; A, Guo; Wang, Yongjun

doi:10.18632/oncotarget.13739

Cited by 55 publications

(46 citation statements)

References 45 publications

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“…Many questions remain as to how microglia and astrocytes interact with each other to influence neuronal survival during cytotoxic events (71)(72)(73)(74). While our evidence here suggests minocycline inhibited microglial activation (but not astrocyte activation) and reduced cell death, the specific contributions of individual cell types to pro-and anti-inflammatory gene expression are not completely clear.…”

Section: Discussionmentioning

confidence: 62%

Minocycline Has Anti-inflammatory Effects and Reduces Cytotoxicity in an Ex Vivo Spinal Cord Slice Culture Model of West Nile Virus Infection

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Clarke

et al. 2017

J Virol

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West Nile virus (WNV) is a neurotropic flavivirus that can cause significant neurological disease. Mouse models of WNV infection demonstrate that a proinflammatory environment is induced within the central nervous system (CNS) after WNV infection, leading to entry of activated peripheral immune cells. We utilized spinal cord slice cultures (SCSC) to demonstrate that anti-inflammatory mechanisms may also play a role in WNV-induced pathology and/or recovery. Microglia are a type of macrophage that function as resident CNS immune cells. Similar to mouse models, infection of SCSC with WNV induces the upregulation of proinflammatory genes and proteins that are associated with microglial activation, including the microglial activation marker Iba1 and CC motif chemokines CCL2, CCL3, and CCL5. This suggests that microglia assume a proinflammatory phenotype in response to WNV infection similar to the proinflammatory (M1) activation that can be displayed by other macrophages. We now show that the WNV-induced expression of these and other proinflammatory genes was significantly decreased in the presence of minocycline, which has antineuroinflammatory properties, including the ability to inhibit proinflammatory microglial responses. Minocycline also caused a significant increase in the expression of anti-inflammatory genes associated with alternative anti-inflammatory (M2) macrophage activation, including interleukin 4 (IL-4), IL-13, and FIZZ1. Minocycline-dependent alterations to M1/M2 gene expression were associated with a significant increase in survival of neurons, microglia, and astrocytes in WNV-infected slices and markedly decreased levels of inducible nitric oxide synthase (iNOS). These results demonstrate that an anti-inflammatory environment induced by minocycline reduces viral cytotoxicity during WNV infection in CNS tissue. West Nile virus (WNV) causes substantial morbidity and mortality, with no specific therapeutic treatments available. Antiviral inflammatory responses are a crucial component of WNV pathology, and understanding how they are regulated is important for tailoring effective treatments. Proinflammatory responses during WNV infection have been extensively studied, but anti-inflammatory responses (and their potential protective and reparative capabilities) following WNV infection have not been investigated. Minocycline induced the expression of genes associated with the anti-inflammatory (M2) activation of CNS macrophages (microglia) in WNV-infected SCSC while inhibiting the expression of genes associated with proinflammatory (M1) macrophage activation and was protective for multiple CNS cell types, indicating its potential use as a therapeutic reagent. This culture system can uniquely address the ability of CNS parenchymal cells (neurons, astrocytes, and microglia) to respond to minocycline and to modulate the inflammatory environment and cytotoxicity in response to WNV infection without peripheral immune cell involvement.

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Section: Discussionmentioning

confidence: 62%

Minocycline Has Anti-inflammatory Effects and Reduces Cytotoxicity in an Ex Vivo Spinal Cord Slice Culture Model of West Nile Virus Infection

Quick

Seitz

Clarke

et al. 2017

J Virol

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“…In this study, we demonstrate for the first time, that MIF alters baseline functional properties of hippocampal CA1 pyramidal neurons (Figure 1), and changes the kinetics of pharmacologicallyevoked NMDA responses in the apical dendrites of these neurons (Figure 3). MIF is known to be involved in several inflammatory and trophic responses, via its role in modulating signaling mechanisms that are regulated by TLR4, p53 and CD74 signaling [11,[28][29][30][31][32][33][34][35][36][37][38][39][40]. While there is evidence showing the involvement of MIF in inflammatory pathways, as well as evidence for MIF effects on…”

Section: Discussionmentioning

confidence: 99%

“…Some of the functions of MIF in the immune system and brain have been previously explored. In an innate immune response, MIF binds to the CD74 receptor complex, along with co-stimulatory factor CD44, initiating downstream signaling cascades and facilitating the immune response [11,[28][29][30][31][32][33][34][35][36][37][38][39][40]. The MIF/CD74 signaling complex is also conserved in microglia and astrocytes.…”

Section: Introductionmentioning

confidence: 99%

Macrophage Migration Inhibitory Factor Alters Functional Properties of CA1 Hippocampal Neurons in Mouse Brain Slices

Bancroft

Srinivasan

Shapiro

2019

IJMS

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Neuroinflammation is implicated in a host of neurological insults, such as traumatic brain injury (TBI), ischemic stroke, Alzheimer’s disease, Parkinson’s disease, and epilepsy. The immune response to central nervous system (CNS) injury involves sequelae including the release of numerous cytokines and chemokines. Macrophage migration inhibitory factor (MIF), is one such cytokine that is elevated following CNS injury, and is associated with the prognosis of TBI, and ischemic stroke. MIF has been identified in astrocytes and neurons, and some of the trophic actions of MIF have been related to its direct and indirect actions on astrocytes. However, the potential modulation of CNS neuronal function by MIF has not yet been explored. This study tests the hypothesis that MIF can directly influence hippocampal neuronal function. MIF was microinjected into the hippocampus and the genetically encoded calcium indicator, GCaMP6f, was used to measure Ca2+ events in acute adult mouse brain hippocampal slices. Results demonstrated that a single injection of 200 ng MIF into the hippocampus significantly increased baseline calcium signals in CA1 pyramidal neuron somata, and altered calcium responses to N-methyl-d-aspartate (NMDA) + D-serine in pyramidal cell apical dendrites located in the stratum radiatum. These data are the first to show direct effects of MIF on hippocampal neurons and on NMDA receptor function. Considering that MIF is elevated after brain insults such as TBI, the data suggest that, in addition to the previously described role of MIF in astrocyte reactivity, elevated MIF can have significant effects on neuronal function in the hippocampus.

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“…On the other hand, Su et al (25) found that PLA2G2A was involved in the astrocyte-mediated inflammatory response through a transcriptome study, indicating that PLA2G2A may be functionally associated with central nervous system homeostasis. Notably, it has been well documented that RBM3 serves a critical role in the neuroprotective effect of synaptic loss (4).…”

Section: Discussionmentioning

confidence: 99%

Impact of RNA‑binding motif 3 expression on the whole transcriptome of prostate cancer cells: An RNA sequencing study

Dong

Zhang

et al. 2018

Oncol Rep

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RNA‑binding motif 3 (RBM3) is a cold‑shock protein that has been previously shown to attenuate cancer stem cell‑like features in prostate cancer (PCa) cells. However, the mechanism underlying RBM3 regulation in PCa cells is largely unknown. The present study investigated the impact of RBM3 expression on the whole transcriptome of PCa cells using high‑throughput RNA sequencing (RNA‑seq). Differentially expressed genes (DEGs) that were identified through RNA‑seq were applied to Gene Ontology (GO), pathway analysis, pathway‑action networks and protein‑protein interaction network analysis. GO and pathway ananlyses showed that RBM3 expression was associated with several metabolism pathways. Combining GO analysis and pathway analysis, certain DEGs, including phospholipase A2 group IIA (PLA2G2A), PLA2G2F, PLA2G4C, endothelin 1, cytochrome P450 family 2 subfamily B member 6, G protein subunit γ5, nitric oxide synthase 3 and CD38 molecule, were shown to be closely associated with RBM3 regulation in PCa cells. Furthermore, the changes in expression of selected genes upon RBM3‑knockdown in RNA‑seq were confirmed by separate reverse transcription‑quantitative‑polymerase chain reaction, validating the results of RNA‑seq. Thus, the present study provides a series of valuable reference genes and pathways for the future study of the pathogenic role of RBM3 in the development of PCa.

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Macrophage migration inhibitory factor activates inflammatory responses of astrocytes through interaction with CD74 receptor

Cited by 55 publications

References 45 publications

Minocycline Has Anti-inflammatory Effects and Reduces Cytotoxicity in an Ex Vivo Spinal Cord Slice Culture Model of West Nile Virus Infection

Minocycline Has Anti-inflammatory Effects and Reduces Cytotoxicity in an Ex Vivo Spinal Cord Slice Culture Model of West Nile Virus Infection

Macrophage Migration Inhibitory Factor Alters Functional Properties of CA1 Hippocampal Neurons in Mouse Brain Slices

Impact of RNA‑binding motif 3 expression on the whole transcriptome of prostate cancer cells: An RNA sequencing study

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