Inhibition of TRPM7 Channels Reduces Degranulation and Release of Cytokines in Rat Bone Marrow-Derived Mast Cells

Huang, Lixiang; Ng, Ngai-Mui; Chen, Ming; Lin, Xiaoling; Tang, Tiantian; Chen, Huihua; Cheng, Yang; Jiang, Shanping

doi:10.3390/ijms150711817

Cited by 27 publications

(32 citation statements)

References 34 publications

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“…Inhibition of the TRPM7 channel via siRNA reduced degranulation and cytokine release in rat bone marrow‐derived mast cells (Huang et al . ). The closely related channel–enzyme TRPM6, however, is not expressed in human (Wykes et al .…”

Section: Discussionmentioning

confidence: 97%

TRPM7 kinase activity regulates murine mast cell degranulation

Zierler

Sumoza-Toledo

Suzuki

et al. 2016

The Journal of Physiology

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Key pointsr The Mg 2+ and Ca 2+ conducting transient receptor potential melastatin 7 (TRPM7) channel-enzyme (chanzyme) has been implicated in immune cell function.r Mice heterozygous for a TRPM7 kinase deletion are hyperallergic, while mice with a single point mutation at amino acid 1648, silencing kinase activity, are not.r As mast cell mediators trigger allergic reactions, we here determine the function of TRPM7 in mast cell degranulation and histamine release.r Our data establish that TRPM7 kinase activity regulates mast cell degranulation and release of histamine independently of TRPM7 channel function.r Our findings suggest a regulatory role of TRPM7 kinase activity on intracellular Ca 2+ and extracellular Mg 2+ sensitivity of mast cell degranulation.Abstract Transient receptor potential melastatin 7 (TRPM7) is a divalent ion channel with a C-terminally located α-kinase. Mice heterozygous for a TRPM7 kinase deletion (TRPM7 +/ K ) are hypomagnesaemic and hyperallergic. In contrast, mice carrying a single point mutation at amino acid 1648, which silences TRPM7 kinase activity (TRPM7 KR ), are not hyperallergic and are resistant to systemic magnesium (Mg 2+ ) deprivation. Since allergic reactions are triggered by mast cell-mediated histamine release, we investigated the function of TRPM7 on mast cell degranulation and histamine release using wild-type (TRPM7 +/+ ), TRPM7 +/ K and TRPM7 KR mice. We found that degranulation and histamine release proceeded independently of TRPM7 channel function. Furthermore, extracellular Mg 2+ assured unperturbed IgE-DNP-dependent exocytosis, independently of TRPM7. However, impairment of TRPM7 kinase function suppressed IgE-DNP-dependent exocytosis, slowed the cellular degranulation rate, and diminished the sensitivity to intracellular calcium (Ca 2+ ) in G protein-induced exocytosis. In addition, G protein-coupled receptor (GPCR) stimulation revealed strong suppression of histamine release, whereas removal of extracellular Mg 2+ caused the phenotype to revert. We conclude that the TRPM7 kinase activity regulates murine mast cell degranulation by changing its sensitivity to intracellular Ca 2+ and affecting granular mobility and/or histamine contents.

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Section: Discussionmentioning

confidence: 97%

TRPM7 kinase activity regulates murine mast cell degranulation

Zierler

Sumoza-Toledo

Suzuki

et al. 2016

The Journal of Physiology

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“…That is, in situations of magnesium deficiency, calcium competes with magnesium and enters the cells. 51,52 Magnesium deficiency appears to increase the production of free radicals and the sensitivity of cells to the attack of reactive oxygen species. 53,54 Hypomagnesemia favors the infiltration of neutrophils and macrophages in the affected cells, which potentiates the activity of the enzyme nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase), increasing the production of the superoxide radical.…”

Section: Metabolic and Physiological Aspects Of Magnesiummentioning

confidence: 99%

Hypomagnesemia and its relation with chronic low-grade inflammation in obesity

Oliveira

Cruz

Silva³

et al. 2017

Rev. Assoc. Med. Bras.

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“…Genetic or pharmacological inhibition of TRPM7 significantly decreased β-hexosaminidase activity and secretion of histamine as well as the release of the pro-inflammatory cytokines IL-6, IL-13 and TNF-α in the asthmatic group compared to the control group. The authors conclude that inhibition of TRPM7 reduces mast cell degranulation and cytokine release (49). However, the question remained, whether kinase and/or channel activity were responsible for the observed phenotype.…”

Section: The Channel-kinase Trpm7 In Immune Cell Signallingmentioning

confidence: 99%

The Channel-Kinase TRPM7 as Novel Regulator of Immune System Homeostasis

Nadolni¹,

Zierler²

2018

Preprint

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The enzyme-coupled transient receptor potential channel subfamily M member 7, TRPM7, has been associated with immunity and immune cell signalling. Here, we review the role of this remarkable signalling protein in lymphocyte proliferation, differentiation, activation and survival. We also discuss its role in mast cell, neutrophil and macrophage function and highlight the potential of TRPM7 to regulate immune system homeostasis. Further, we shed light on how the cellular signalling cascades involving TRPM7 channel and/or kinase activity culminate in pathologies as diverse as allergic hypersensitivity, arterial thrombosis, and graft versus host disease (GVHD), stressing the need for TRPM7 specific pharmacological modulators.

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Inhibition of TRPM7 Channels Reduces Degranulation and Release of Cytokines in Rat Bone Marrow-Derived Mast Cells

Cited by 27 publications

References 34 publications

TRPM7 kinase activity regulates murine mast cell degranulation

TRPM7 kinase activity regulates murine mast cell degranulation

Hypomagnesemia and its relation with chronic low-grade inflammation in obesity

The Channel-Kinase TRPM7 as Novel Regulator of Immune System Homeostasis

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