Induction of Microglial Activation by Mediators Released from Mast Cells

Zhang, Xiang; Wang, Yiming; Dong, Huijuan; Xu, Ying; Shu, Zhang

doi:10.1159/000443093

Cited by 77 publications

(53 citation statements)

References 41 publications

(48 reference statements)

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“…Our data further demonstrate that downstream signal pathways, namely, PLC and PIP2 were involved in the effects of PAR2 regulation of TRPA1 currents. MAPK and PI3K/AKT are also likely involved in the process of PAR2 activation [28]. Consistent with these findings, data from our present study using a whole animal preparation also demonstrated that blocking the PAR2 signal significantly attenuated the BP response evoked by static muscle contraction and SNA and BP responses evoked by TRPA1 stimulation to a greater degree in occluded rats than in control rats.…”

Section: Discussionsupporting

confidence: 90%

Proteinase-Activated Receptor-2 Sensitivity of Amplified TRPA1 Activity in Skeletal Muscle Afferent Nerves and Exercise Pressor Reflex in Rats with Femoral Artery Occlusion

Xing

2017

Cell Physiol Biochem

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Background/Aims: Limb ischemia occurs in peripheral artery disease (PAD). Sympathetic nerve activity (SNA) that regulates blood flow directed to the ischemic limb is exaggerated during exercise in this disease, and transient receptor potential channel A1 (TRPA1) in thin-fiber muscle afferents contributes to the amplified sympathetic response. The purpose of the present study was to determine the role of proteinase-activated receptor-2 (PAR2) in regulating abnormal TRPA1 function and the TRPA1-mediated sympathetic component of the exercise pressor reflex. Methods: A rat model of femoral artery ligation was employed to study PAD. Dorsal root ganglion (DRG) tissues were obtained to examine the protein levels of PAR2 using western blot analysis. Current responses induced by activation of TRPA1 in skeletal muscle DRG neurons were characterized using whole-cell patch clamp methods. The blood pressure response to static exercise (i.e., muscle contraction) and stimulation of TRPA1 was also examined after a blockade of PAR2. Results: The expression of PAR2 was amplified in DRG neurons of the occluded limb, and PAR2 activation with SL-NH2 (a PAR2 agonist) increased the amplitude of TRPA1 currents to a greater degree in DRG neurons of the occluded limb. Moreover, FSLLRY-NH2 (a PAR antagonist) injected into the arterial blood supply of the hindlimb muscles significantly attenuated the pressor response to muscle contraction and TRPA1 stimulation in rats with occluded limbs. Conclusions: The PAR2 signal in muscle sensory nerves contributes to the amplified exercise pressor reflex via TRPA1 mechanisms in rats with femoral artery ligation. These findings provide a pathophysiological basis for autonomic responses during exercise activity in PAD, which may potentially aid in the development of therapeutic approaches for improvement of blood flow in this disease.

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Section: Discussionsupporting

confidence: 90%

Proteinase-Activated Receptor-2 Sensitivity of Amplified TRPA1 Activity in Skeletal Muscle Afferent Nerves and Exercise Pressor Reflex in Rats with Femoral Artery Occlusion

Xing

2017

Cell Physiol Biochem

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“…Mast cell secreted cytokines have a pivotal role in the pathogenesis of allergic disease and inflammation [23, 24]. Interleukin-13 (IL-13) and monocyte chemoattractant protein 1 (MCP-1) are two cytokines among those produced by human and mouse mast cells.…”

Section: Discussionmentioning

confidence: 99%

Modulation of Mast Cell Toll-Like Receptor 3 Expression and Cytokines Release by Histamine

Xie¹,

Wang²,

Peng³

et al. 2018

Cell Physiol Biochem

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Background/Aims: As a major inflammatory molecule released from mast cell activation, histamine has been reported to regulate TLRs expression and cytokine production in inflammatory cells present in the microenvironment. In this study, we determined the ability of histamine to modulate TLRs expression and cytokine production in mast cells. Methods: HMC-1 and P815 cells were exposed to various concentrations of histamine in the presence or absence of histamine antagonist for 2, 6 or 16 h. The effect of histamine on the expression of TLR3 protein and mRNA was analyzed by flow cytometry、 RT-PCR and immunofluorescent microscopy. Furthermore, we also examined the effect of histamine on the secretion of MCP-1 and IL-13 from mast cells by ELISA. Results: The amplification of TLR3 mRNA and protein expression in mast cells was observed after incubation with histamine, which was accompanied by increasing secretion of IL-13 and MCP-1 via H1 receptor. The signaling pathways of PI3K/ Akt and Erk1/2/MAPK contributed to these induction effects. Conclusion: These results demonstrate that histamine up-regulates the expression of TLR3 and secretion of IL-13 and MCP-1 in mast cells, thus identifying a new mechanism for the histamine inducing allergic response.

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“…Mast cells interact/cross-talk with astrocytes, neurons, microglia and oligodendrocytes in the pathogenesis of neurodegenerative diseases (Skaper and Facci, 2012; Skaper et al, 2012; Skaper et al, 2013a; Frieri et al, 2015). It has been reported that mast cells but not the microglia were the first responders in the brain injury (Jin et al, 2009) and also release TNF-α before the other cells, indicating its immediate response in the brain (Zhang et al, 2016). Mast cell protease tryptase is an important serine-protease and plays an important role in inflammation.…”

Section: Discussionmentioning

confidence: 99%

Cross-Talk between Glia, Neurons and Mast Cells in Neuroinflammation Associated with Parkinson’s Disease

Kempuraj

Selvakumar

Zaheer

et al. 2017

J Neuroimmune Pharmacol

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Parkinson’s disease (PD) is a progressive movement disorder characterized by neuroinflammation and dopaminergic neurodegeneration in the brain. 1-methyl-4-phenylpyridinium (MPP+), a metabolite of the parkinsonian neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induces the release of inflammatory mediators from glial cells and neurons. Glia maturation factor (GMF), a brain proinflammatory protein, MPP+, and mast cell-derived inflammatory mediators induce neurodegeneration which eventually leads to PD. However, the precise mechanisms underlying interaction between glial cells, neurons and mast cells in PD still remain elusive. In the present study, mouse bone marrow-derived mast cells (BMMCs) and mouse fetal brain-derived mixed glia/neurons, astrocytes and neurons were incubated with MPP+, GMF and mast cell-derived inflammatory mediators mouse mast cell protease-6 (MMCP-6), MMCP-7 or tryptase/brain-specific serine protease-4 (tryptase/BSSP-4). Inflammatory mediators released from these cells in the culture medium were quantitated by enzyme-linked immunosorbent assay. Neurodegeneration was quantified by measuring total neurite outgrowth following microtubule-associated protein-2 immunocytochemistry. MPP+− induced significant neurodegeneration with reduced total neurite outgrowth. MPP+− induced the release of tryptase/BSSP-4 from the mouse mast cells, and tryptase/BSSP-4 induced chemokine (C-C motif) ligand 2 (CCL2) release from astrocytes and glia/neurons. Overall our results suggest that MPP+, GMF, MMCP-6 or MMCP-7 stimulate glia/neurons, astrocytes or neurons to release CCL2 and matrix metalloproteinase-3. Additionally, CD40L expression is increased in BMMCs after incubation with MPP+ in a co-culture system consisting of BMMCs and glia/neurons. We propose that mast cell interaction with glial cells and neurons during neuroinflammation can be explored as a new therapeutic target for PD.

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Induction of Microglial Activation by Mediators Released from Mast Cells

Cited by 77 publications

References 41 publications

Proteinase-Activated Receptor-2 Sensitivity of Amplified TRPA1 Activity in Skeletal Muscle Afferent Nerves and Exercise Pressor Reflex in Rats with Femoral Artery Occlusion

Proteinase-Activated Receptor-2 Sensitivity of Amplified TRPA1 Activity in Skeletal Muscle Afferent Nerves and Exercise Pressor Reflex in Rats with Femoral Artery Occlusion

Modulation of Mast Cell Toll-Like Receptor 3 Expression and Cytokines Release by Histamine

Cross-Talk between Glia, Neurons and Mast Cells in Neuroinflammation Associated with Parkinson’s Disease

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