Suppression of Brain Mast Cells Degranulation Inhibits Microglial Activation and Central Nervous System Inflammation

Dong, Huijuan; Zhang, Xiang; Wang, Yiming; Zhou, Xiqiao; Qian, Yanning; Zhang, Shu

doi:10.1007/s12035-016-9720-x

Cited by 72 publications

(62 citation statements)

References 39 publications

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“…Our results show that several neural cell types express receptors for histamine, one of the main molecules released by MCs and a mediator of inflammation and that histamine exacerbates excitotoxic cell death in primary neuronal cultures. Furthermore, cromoglycate, an inhibitor of MC degranulation, increased the numbers of toluidine blue‐positive MCs when administered peripherally before TBI, as had been previously reported in rats (Strbian et al, ; Dong et al, ). This suggests that cromoglycate effectively inhibited degranulation of the MCs that infiltrated the brain after TBI.…”

Section: Discussionsupporting

confidence: 78%

Contribution of mast cells to injury mechanisms in a mouse model of pediatric traumatic brain injury

Moretti

Chhor

Bettati

et al. 2016

J of Neuroscience Research

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The cognitive and behavioral deficits caused by traumatic brain injury (TBI) to the immature brain are more severe and persistent than injuries to the adult brain. Understanding this developmental sensitivity is critical because children under 4 years of age of sustain TBI more frequently than any other age group. One of the first events after TBI is the infiltration and degranulation of mast cells (MCs) in the brain, releasing a range of immunomodulatory substances; inhibition of these cells is neuroprotective in other types of neonatal brain injury. This study investigates for the first time the role of MCs in mediating injury in a P7 mouse model of pediatric contusion-induced TBI. We show that various neural cell types express histamine receptors and that histamine exacerbates excitotoxic cell death in primary cultured neurons. Cromoglycate, an inhibitor of MC degranulation, altered the inflammatory phenotype of microglia activated by TBI, reversing several changes but accentuating others, when administered before TBI. However, without regard to the time of cromoglycate administration, inhibiting MC degranulation did not affect cell loss, as evaluated by ventricular dilatation or cleaved caspase-3 labeling, or the density of activated microglia, neurons, or myelin. In double-heterozygous cKit mutant mice lacking MCs, this overall lack of effect was confirmed. These results suggest that the role of MCs in this model of pediatric TBI is restricted to subtle effects and that they are unlikely to be viable neurotherapeutic targets. © 2016 Wiley Periodicals, Inc.

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Section: Discussionsupporting

confidence: 78%

Contribution of mast cells to injury mechanisms in a mouse model of pediatric traumatic brain injury

Moretti

Chhor

Bettati

et al. 2016

J of Neuroscience Research

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“…We found that the MAPK and AKT signalling pathways were involved in MC-induced microglial activation in vivo [24]. To confirm this finding, we investigated these signalling pathways in vitro.…”

Section: The Mapk and Akt Pathways Mediated Mc-induced Microglial Actmentioning

confidence: 68%

Induction of Microglial Activation by Mediators Released from Mast Cells

Zhang¹,

Wang²,

Dong³

et al. 2016

Cell Physiol Biochem

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Background/Aims: Microglia are the resident immune cells in the brain and play a pivotal role in immune surveillance in the central nervous system (CNS). Brain mast cells are activated in CNS disorders and induce the release of several mediators. Thus, brain mast cells, rather than microglia, are the “first responders” due to injury. However, the functional aspects of mast cell-microglia interactions remain uninvestigated. Methods: Conditioned medium from activated HMC-1 cells induces microglial activation similar to co-culture of microglia with HMC-1 cells. Primary cultured microglia were examined by flow cytometry analysis and confocal microscopy. TNF- alpha and IL-6 were measured with commercial ELISA kits. Cell signalling was analysed by Western blotting. Results: In the present study, we found that the conditioned medium from activated HMC-1 cells stimulated microglial activation and the subsequent production of the pro-inflammatory factors TNF-α and IL-6. Co-culture of microglia and HMC-1 cells with corticotropin-releasing hormone (CRH) for 24, 48 and 72 hours increased TNF-α and IL-6 production. Antagonists of histamine receptor 1 (H₁R), H₄R, proteinase-activated receptor 2 (PAR2) or Toll-like receptor 4 (TLR4) reduced HMC-1-induced pro-inflammatory factor production and MAPK and PI3K/AKT pathway activation. Conclusions: These results imply that activated mast cells trigger microglial activation. Interactions between mast cells and microglia could constitute a new and unique therapeutic target for CNS inflammation-related diseases.

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“…CX3CL1 could, in turn, stimulate microglia thus establishing positive feedback. Therefore it is possible that chemokines and cytokines secreted by activated microglia can be involved in establishing a state of neuronal hyperactivity and central sensitization [13,[43][44][45][46]. Overall, microglia, through these mechanisms, can contribute to brain inflammation and to the pathogenesis of different brain disorders [41,[47][48][49][50][51][52].…”

Section: Inflammatory Mediators and Innate Immunity In The Generationmentioning

confidence: 99%

T Cell Subpopulations in the Physiopathology of Fibromyalgia: Evidence and Perspectives

Banfi

Diani

Pigatto

et al. 2020

IJMS

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Fibromyalgia is one of the most important "rheumatic" disorders, after osteoarthritis. The etiology of the disease is still not clear. At the moment, the most defined pathological mechanism is the alteration of central pain pathways, and emotional conditions can trigger or worsen symptoms. Increasing evidence supports the role of mast cells in maintaining pain conditions such as musculoskeletal pain and central sensitization. Importantly, mast cells can mediate microglia activation through the production of proinflammatory cytokines such as IL-1β, IL-6, and TNFα. In addition, levels of chemokines and proinflammatory cytokines are enhanced in serum and could contribute to inflammation at systemic level. Despite the well-characterized relationship between the nervous system and inflammation, the mechanism that links the different pathological features of fibromyalgia, including stress-related manifestations, central sensitization, and dysregulation of the innate and adaptive immune responses is largely unknown. This review aims to provide an overview of the current understanding of the role of adaptive immune cells, in particular T cells, in the physiopathology of fibromyalgia. It also aims at linking the latest advances emerging from basic science to envisage new perspectives to explain the role of T cells in interconnecting the psychological, neurological, and inflammatory symptoms of fibromyalgia.

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Suppression of Brain Mast Cells Degranulation Inhibits Microglial Activation and Central Nervous System Inflammation

Cited by 72 publications

References 39 publications

Contribution of mast cells to injury mechanisms in a mouse model of pediatric traumatic brain injury

Contribution of mast cells to injury mechanisms in a mouse model of pediatric traumatic brain injury

Induction of Microglial Activation by Mediators Released from Mast Cells

T Cell Subpopulations in the Physiopathology of Fibromyalgia: Evidence and Perspectives

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