TNF Increases Expression of IL-4 and PARs in Mast Cells

Zhang, Huiyun; Yang, Haiwei; He, Shaoheng

doi:10.1159/000320556

Cited by 34 publications

(25 citation statements)

References 42 publications

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“…In vitro, mast cell tryptase can activate microglia via PAR2 and PAR2 expression on mast cells can be increased by tumour necrosis factor (Zhang et al, 2010;Zhang et al, 2012). There were very low numbers of mast cells in the brain regions examined in this study.…”

Section: Mast Cellsmentioning

confidence: 54%

Altered Expression of Brain Proteinase-Activated Receptor-2, Trypsin-2 and Serpin Proteinase Inhibitors in Parkinson’s Disease

et al. 2015

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In neurologically normal brain expression of proteinase-activated receptor-2, activating proteinases and proteinase inhibitors was found in neurons and microglia and did not specifically associate with regions prone to neurodegeneration in Parkinson's disease. InParkinson's disease brain, alterations in the amount of immunoreactivity for proteinaseactivated receptor-2, trypsin-2 and both serpin proteinase inhibitors were found throughout the brain. In neurons, there was a decrease in neurons positive for proteinase inhibitors with increasing Braak α-synuclein stage in the dorsal motor nucleus, locus coeruleus, substantia nigra and primary motor cortex. In contrast, in the cingulate cortex, proteinase-activated receptor-2 expression had a positive correlation to increase with higher Braak α-synuclein stage rating and serpin-A13 was increased in early Parkinson's disease cases compared to controls. In microglia, increased expression occurred for the serpins (dorsal motor nucleus of vagus and substantia nigra), trypsin-2 (dorsal motor nucleus of vagus and primary motor cortex) and proteinase-activated receptor-2 (locus coeruleus and cingulate cortex) that progressively increased with advancing Parkinson's disease severity.In cingulate cortex, the covariate dyskinesia had a significant effect on the the adjusted means for trypsin-2 labelled neurons and microglia and the covariate psychosis had a significant effect on neurons labelled with serpin-A5. While in primary motor cortex, the covariate dyskinesia had a significant effect on the the adjusted means for neurons labelled with serpin-A5, serpin-A13 and trypsin-2. Analysis of Parkinson's disease cases found that serpin and trypsin-2 expression in midbrain and cerebral cortex was different in cases with dyskinesia and psychosis compared to those with no treatment induced side-effects. This study showed that there was altered expression in brain of proteinase-activated receptor-2 and some proteins that can control its function in Parkinson's disease. Given the role of PAR2 expression in Parkinson's disease 3 proteinase-activated receptor-2 in neuroinflammation, drugs that mitigate these changes could be neuroprotective when administered to patients with Parkinson's disease.

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Section: Mast Cellsmentioning

confidence: 54%

Altered Expression of Brain Proteinase-Activated Receptor-2, Trypsin-2 and Serpin Proteinase Inhibitors in Parkinson’s Disease

et al. 2015

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“…IL-33 binds to MC receptors and triggers the production of monocyte chemo-attractant protein 1, IL-6 and IL-13, which in turn may regulate microglial activity. Similarly, tryptase released from MCs activates the microglial PAR-2 receptors, thereby initiating the production of inflammatory mediators such as TNF-α, IL-6, and ROS that consequently upregulate the expression of PAR2 receptors on MCs [15,42]. Our previous studies showed the presence of tryptase and histamine receptors on the surface of microglia.…”

Section: Discussionmentioning

confidence: 90%

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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“…For example, interleukin- (IL-) 12 is able to downregulate PAR-2 expression [20], and IL-29 decreases PAR-1 expression [29] on P815 mast cells. On the other hand, granulocyte-macrophage colony-stimulating factor (GM-CSF) enhances expression of PAR-4 [30], tumor necrosis factor (TNF) [31] upregulates PAR-2 and PAR-4 expression, and RANTES increases expression of PAR-1 on P815 mast cells [32]. TNF also elevates PAR-2 expression on HMC-1 mast cells [23], and IL-12 upregulates PAR-4 expression on MC/9 mast cells [20].…”

Section: Expression Of Pars On Inflammatory Cellsmentioning

confidence: 99%

Evaluation on Potential Contributions of Protease Activated Receptors Related Mediators in Allergic Inflammation

Zhang

Zeng

2014

Mediators of Inflammation

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Protease activated receptors (PARs) have been recognized as a distinctive four-member family of seven transmembrane G protein-coupled receptors (GPCRs) that can be cleaved by certain serine proteases. In recent years, there has been considerable interest in the role of PARs in allergic inflammation, the fundamental pathologic changes of allergy, but the potential roles of PARs in allergy remain obscure. Since many of these proteases are produced and actively involved in the pathologic process of inflammation including exudation of plasma components, inflammatory cell infiltration, and tissue damage and repair, PARs appear to make important contribution to allergy. The aim of the present review is to summarize the expression of PARs in inflammatory and structural cells, the influence of agonists or antagonists of PARs on cell behavior, and the involvement of PARs in allergic disorders, which will help us to better understand the roles of serine proteases and PARs in allergy.

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TNF Increases Expression of IL-4 and PARs in Mast Cells

Cited by 34 publications

References 42 publications

Altered Expression of Brain Proteinase-Activated Receptor-2, Trypsin-2 and Serpin Proteinase Inhibitors in Parkinson’s Disease

Altered Expression of Brain Proteinase-Activated Receptor-2, Trypsin-2 and Serpin Proteinase Inhibitors in Parkinson’s Disease

Induction of Microglial Activation by Mediators Released from Mast Cells

Evaluation on Potential Contributions of Protease Activated Receptors Related Mediators in Allergic Inflammation

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