C5a/C5aR Pathway Plays a Vital Role in Brain Inflammatory Injury via Initiating Fgl-2 in Intracerebral Hemorrhage

Yuan, Bangqing; Fu, Fenlan; Huang, Shaokuan; Lin, Chuangan; Yang, Guang; Ma, Kunlong; Shi, Hui; Yang, Zhao

doi:10.1007/s12035-016-0141-7

Cited by 26 publications

(17 citation statements)

References 40 publications

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“…Complementary expression of C5a receptor on activated mast cells provides a strong chemoattractant signal toward C5a peptide (Pundir et al, 2015 ). The C5a-C5a receptor pathway plays a vital role in brain inflammatory injury, including intracerebral hemorrhage (Young et al, 2013 ; Yuan et al, 2017 ). In the context of AD, the central complement factor C3 secreted from astrocytes interacts with microglial C3a receptor to mediate β-amyloid pathology and neuroinflammation in AD mouse models (Lian et al, 2015 , 2016 ).…”

Section: Neuroinflammation Is Amplified By Mast Cell—glia and Glia—glmentioning

confidence: 99%

An Inflammation-Centric View of Neurological Disease: Beyond the Neuron

Skaper

Facci

Zusso

et al. 2018

Front. Cell. Neurosci.

336

240

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Inflammation is a complex biological response fundamental to how the body deals with injury and infection to eliminate the initial cause of cell injury and effect repair. Unlike a normally beneficial acute inflammatory response, chronic inflammation can lead to tissue damage and ultimately its destruction, and often results from an inappropriate immune response. Inflammation in the nervous system (“neuroinflammation”), especially when prolonged, can be particularly injurious. While inflammation per se may not cause disease, it contributes importantly to disease pathogenesis across both the peripheral (neuropathic pain, fibromyalgia) and central [e.g., Alzheimer disease, Parkinson disease, multiple sclerosis, motor neuron disease, ischemia and traumatic brain injury, depression, and autism spectrum disorder] nervous systems. The existence of extensive lines of communication between the nervous system and immune system represents a fundamental principle underlying neuroinflammation. Immune cell-derived inflammatory molecules are critical for regulation of host responses to inflammation. Although these mediators can originate from various non-neuronal cells, important sources in the above neuropathologies appear to be microglia and mast cells, together with astrocytes and possibly also oligodendrocytes. Understanding neuroinflammation also requires an appreciation that non-neuronal cell—cell interactions, between both glia and mast cells and glia themselves, are an integral part of the inflammation process. Within this context the mast cell occupies a key niche in orchestrating the inflammatory process, from initiation to prolongation. This review will describe the current state of knowledge concerning the biology of neuroinflammation, emphasizing mast cell-glia and glia-glia interactions, then conclude with a consideration of how a cell's endogenous mechanisms might be leveraged to provide a therapeutic strategy to target neuroinflammation.

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Section: Neuroinflammation Is Amplified By Mast Cell—glia and Glia—glmentioning

confidence: 99%

An Inflammation-Centric View of Neurological Disease: Beyond the Neuron

Skaper

Facci

Zusso

et al. 2018

Front. Cell. Neurosci.

336

240

View full text Add to dashboard Cite

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“…ICH-induced microglial activation, as assessed by immunoreactivity to an anti-CD11b and anti-CD11c dual-specificity antibody (OX42), was reduced in C3-deficient mice compared with wild-type controls 74 . In C5a receptor knockout mice, proinflammatory cytokine levels were decreased in the acute phase after ICH 75 . Moreover, treatment with the C5a receptor antagonist PMX53 in combination with the thrombin antagonist argatroban resulted in decreased mRNA expression of the M1 markers TNF, IL-6 and iNOS in the mouse ICH brain 76 .…”

Section: Microgliamentioning

confidence: 96%

Modulators of microglial activation and polarization after intracerebral haemorrhage

et al. 2017

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Intracerebral haemorrhage (ICH) is the most lethal subtype of stroke but currently lacks effective treatment. Microglia are among the first non-neuronal cells on the scene during the innate immune response to ICH. Microglia respond to acute brain injury by becoming activated and developing classic M1-like (proinflammatory) or alternative M2-like (anti-inflammatory) phenotypes. This polarization implies as yet unrecognized actions of microglia in ICH pathology and recovery, perhaps involving microglial production of proinflammatory or anti-inflammatory cytokines and chemokines. Furthermore, alternatively activated M2-like microglia might promote phagocytosis of red blood cells and tissue debris, a major contribution to haematoma clearance. Interactions between microglia and other cells modulate microglial activation and function, and are also important in ICH pathology. This Review summarizes key studies on modulators of microglial activation and polarization after ICH, including M1-like and M2-like microglial phenotype markers, transcription factors and key signalling pathways. Microglial phagocytosis, haematoma resolution, and the potential crosstalk between microglia and T lymphocytes, neurons, astrocytes, and oligodendrocytes in the ICH brain are described. Finally, the clinical and translational implications of microglial polarization in ICH are presented, including the evidence that therapeutic approaches aimed at modulating microglial function might mitigate ICH injury and improve brain repair.

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“…Previous studies have shown that ICH can activate MAPK signaling through phosphorylation of ERK1/2, p38 and JNK proteins, leading to in ammatory cytokine production [35]. In addition, phosphorylation of ERK, p38, and JNK is increased in TIPE2-silenced macrophages stimulated with MP.…”

Section: Discussionmentioning

confidence: 91%

Upregulation of TIPE2 attenuates macrophage activation and neuroinflammation after intracerebral hemorrhage in mice

Liu

Wang

et al. 2020

Preprint

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Background: Intracerebral hemorrhage (ICH) is a serious disease with high mortality and morbidity, and effective treatment is limited. A large amount of evidence suggests that the inflammatory response contributes to secondary brain damage following ICH. TIPE2 is an essential negative regulator of both innate and adaptive immunity, and depletion of TIPE2 causes inflammatory disease. However, the possible role of TIPE2 following ICH has not been reported. Methods: In this study, we investigated TIPE2 levels and inflammation in macrophages treated with erythrocyte lysate in vitro, and we observed proinflammatory cytokine production, BBB disruption, cerebral water content and neurological damage in ICH mice in vivo. Results: We found that TIPE2 levels were significantly decreased in erythrocyte lysate-treated macrophages compared to control macrophages. Upregulation of TIPE2 decreased macrophage activation and cytokine production and accelerated brain damage in ICH mice. In addition, upregulation of TIPE2 attenuated proinflammatory cytokine production, BBB disruption, and severe brain inflammation after ICH. Conclusion: The results demonstrated that TIPE2 was negatively correlated with the pathogenesis of ICH, which prevented brain injury and attenuated deleterious inflammatory responses following ICH. TIPE2 might serve as a novel target for ICH therapy.

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C5a/C5aR Pathway Plays a Vital Role in Brain Inflammatory Injury via Initiating Fgl-2 in Intracerebral Hemorrhage

Cited by 26 publications

References 40 publications

An Inflammation-Centric View of Neurological Disease: Beyond the Neuron

An Inflammation-Centric View of Neurological Disease: Beyond the Neuron

Modulators of microglial activation and polarization after intracerebral haemorrhage

Upregulation of TIPE2 attenuates macrophage activation and neuroinflammation after intracerebral hemorrhage in mice

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