scholarly journals A Rapid Shift from Chronic Hyperoxia to Normoxia Induces Systemic Anaphylaxis via Transient Receptor Potential Ankyrin 1 Channels on Mast Cells

2020 ◽  
Vol 205 (11) ◽  
pp. 2959-2967
Author(s):  
Kenshiro Matsuda ◽  
Peter D. Arkwright ◽  
Yasuo Mori ◽  
Masa-aki Oikawa ◽  
Ryo Muko ◽  
...  
Keyword(s):  
Mast Cells ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Systemic Anaphylaxis ◽  
Transient Receptor ◽  
Rapid Shift

scholarly journals Cutaneous Neuroimmune Interactions of TSLP and TRPV4 Play Pivotal Roles in Dry Skin-Induced Pruritus

2021 ◽  
Vol 12 ◽  
Author(s):  
Wook-Joo Lee ◽  
Won-Sik Shim
Keyword(s):  
Mast Cells ◽  
Dorsal Root ◽  
Transient Receptor Potential ◽  
Skin Barrier ◽  
Receptor Potential ◽  
Barrier Dysfunction ◽  
Dry Skin ◽  
Neuroimmune Interactions ◽  
Skin Conditions ◽  
Transient Receptor

Dry skin is a symptom of skin barrier dysfunction that evokes pruritus; however, the cutaneous neuroimmune interactions underlying dry skin-induced pruritus remain unclear. Therefore, we aimed to elucidate the mechanisms underlying dry skin-induced pruritus. To this end, an acetone/ethanol/water (AEW)-induced mouse model of dry skin was used in this study. We observed that the production of thymic stromal lymphopoietin (TSLP) significantly increased in the keratinocytes of AEW mice. Importantly, treatment with an antagonist of transient receptor potential cation channel subfamily V member 4 (TRPV4), HC067047, ameliorated dry skin conditions in AEW mice. The symptoms of dry skin were significantly reduced in Trpv4 knockout (KO) mice following treatment with AEW. The increase in the intracellular calcium levels by TSLP in the dorsal root ganglia (DRG) of Trpv4 KO mice was also significantly attenuated. The spontaneous scratching bouts were significantly decreased in both the HC067047-treated and Trpv4 KO AEW mice. Importantly, the TSLP-dependent release of tryptase from the mast cells was significantly reduced in both the HC067047-treated mice and Trpv4 KO AEW mice. Notably, inhibition of the TSLP-induced signaling pathway in DRG selectively reduced the spontaneous scratching bouts in AEW mice. Overall, the results demonstrated that the cutaneous neuroimmune interactions of TSLP and TRPV4 play pivotal roles in dry skin-induced pruritus.

scholarly journals Essential Role of Mast Cells in the Visceral Hyperalgesia Induced byT. spiralisInfection and Stress in Rats

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Chang-Qing Yang ◽  
Yan-Yu Wei ◽  
Chan-Juan Zhong ◽  
Li-Ping Duan
Keyword(s):  
Mast Cells ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Pcr Analysis ◽  
Signal Pathways ◽  
Transient Receptor Potential Vanilloid ◽  
Visceral Hyperalgesia ◽  
Cold Restraint Stress ◽  
Transient Receptor ◽  
Extracellular Regulated Kinase

Mast cells (MCs) deficient rats (Ws/Ws) were used to investigate the roles of MCs in visceral hyperalgesia. Ws/Ws and wild control (+/+) rats were exposed toT. spiralisor submitted to acute cold restraint stress (ACRS). Levels of proteinase-activated receptor 2 (PAR2) and nerve growth factor (NGF) were determined by immunoblots and RT-PCR analysis, and the putative signal pathways including phosphorylated extracellular-regulated kinase (pERK1/2) and transient receptor potential vanilloid receptor 1 (TRPV1) were further identified. Visceral hyperalgesia triggered by ACRS was observed only in+/+rats. The increased expression of PAR2 and NGF was observed only in+/+rats induced byT. spiralisand ACRS. The activation of pERK1/2 induced by ACRS occurred only in+/+rats. However, a significant increase of TRPV1 induced byT. spiralisand ACRS was observed only in+/+rats. The activation of PAR2 and NGF via both TRPV1 and pERK1/2 signal pathway is dependent on MCs in ACRS-induced visceral hyperalgesia rats.

scholarly journals A TRPV2–PKA Signaling Module for Transduction of Physical Stimuli in Mast Cells

2004 ◽  
Vol 200 (2) ◽  
pp. 137-147 ◽  
Author(s):  
Alexander J. Stokes ◽  
Lori M.N. Shimoda ◽  
Murielle Koblan-Huberson ◽  
Chaker N. Adra ◽  
Helen Turner
Keyword(s):  
Mast Cells ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Functional Coupling ◽  
Transient Receptor Potential Vanilloid ◽  
Functional Responses ◽  
Signaling Mechanism ◽  
Cutaneous Mast Cell ◽  
Transient Receptor

Cutaneous mast cell responses to physical (thermal, mechanical, or osmotic) stimuli underlie the pathology of physical urticarias. In vitro experiments suggest that mast cells respond directly to these stimuli, implying that a signaling mechanism couples functional responses to physical inputs in mast cells. We asked whether transient receptor potential (vanilloid) (TRPV) cation channels were present and functionally coupled to signaling pathways in mast cells, since expression of this channel subfamily confers sensitivity to thermal, osmotic, and pressure inputs. Transcripts for a range of TRPVs were detected in mast cells, and we report the expression, surface localization, and oligomerization of TRPV2 protein subunits in these cells. We describe the functional coupling of TRPV2 protein to calcium fluxes and proinflammatory degranulation events in mast cells. In addition, we describe a novel protein kinase A (PKA)–dependent signaling module, containing PKA and a putative A kinase adapter protein, Acyl CoA binding domain protein (ACBD)3, that interacts with TRPV2 in mast cells. We propose that regulated phosphorylation by PKA may be a common pathway for TRPV modulation.

scholarly journals Mast-Cell Degranulation Induced by Physical Stimuli Involves the Activation of Transient-Receptor-Potential Channel TRPV2

2012 ◽  
pp. 113-124 ◽  
Author(s):  
D. ZHANG ◽  
A. SPIELMANN ◽  
L. WANG ◽  
G. DING ◽  
F. HUANG ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Transient Receptor Potential ◽  
Laser Light ◽  
Receptor Potential ◽  
Ruthenium Red ◽  
Mast Cell Degranulation ◽  
Human Mast Cell ◽  
Physical Stimuli ◽  
Transient Receptor

A characteristic of mast cells is the degranulation in response to various stimuli. Here we have investigated the effects of various physical stimuli in the human mast-cell line HMC-1. We have shown that HMC-1 express the transient receptor potential channels TRPV1, TRPV2 and TRPV4. In the whole-cell patch-clamp configuration, increasing mechanical stress applied to the mast cell by hydrostatic pressure (–30 to –90 cm H2O applied via the patch pipette) induced a current that could be inhibited by 10 µM of ruthenium red. This current was also inhibited by 20 µM SKF96365, an inhibitor that is among TRPV channels specific for the TRPV2. A characteristic of TRPV2 is its activation by high noxious temperature; temperatures exceeding 50 °C induced a similar ruthenium-red-sensitive current. As another physical stimulus, we applied laser light of 640 nm. Here we have shown for the first time that the application of light (at 48 mW for 20 min) induced an SKF96365-sensitive current. All three physical stimuli that led to activation of SKF96365-sensitive current also induced pronounced degranulation in the mast cells, which could be blocked by ruthenium red or SKF96365. The results suggest that TRPV2 is activated by the three different types of physical stimuli. Activation of TRPV2 allows Ca2+ ions to enter the cell, which in turn will induce degranulation. We, therefore, suggest that TRPV2 plays a key role in mast-cell degranulation in response to mechanical, heat and red laser-light stimulation.

Crucial Role of Transient Receptor Potential Ankyrin 1 and Mast Cells in Induction of Nonallergic Airway Hyperreactivity in Mice

2013 ◽  
Vol 187 (5) ◽  
pp. 486-493 ◽  
Author(s):  
Valérie Hox ◽  
Jeroen A. Vanoirbeek ◽  
Yeranddy A. Alpizar ◽  
Sabrina Voedisch ◽  
Ina Callebaut ◽  
...  
Keyword(s):  
Mast Cells ◽  
Crucial Role ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Airway Hyperreactivity ◽  
Transient Receptor

Inositol lipids and TRPC channel activation

2007 ◽  
Vol 74 ◽  
pp. 37-45 ◽  
Author(s):  
James W. Putney
Keyword(s):  
Plasma Membrane ◽  
Phospholipase C ◽  
Transient Receptor Potential ◽  
Calcium Signalling ◽  
Receptor Potential ◽  
Breakdown Product ◽  
Channel Activation ◽  
Inositol Lipids ◽  
Transient Receptor ◽  
Secondary Mechanism

The original hypothesis put forth by Bob Michell in his seminal 1975 review held that inositol lipid breakdown was involved in the activation of plasma membrane calcium channels or ‘gates’. Subsequently, it was demonstrated that while the interposition of inositol lipid breakdown upstream of calcium signalling was correct, it was predominantly the release of Ca2+ that was activated, through the formation of Ins(1,4,5)P3. Ca2+ entry across the plasma membrane involved a secondary mechanism signalled in an unknown manner by depletion of intracellular Ca2+ stores. In recent years, however, additional non-store-operated mechanisms for Ca2+ entry have emerged. In many instances, these pathways involve homologues of the Drosophila trp (transient receptor potential) gene. In mammalian systems there are seven members of the TRP superfamily, designated TRPC1–TRPC7, which appear to be reasonably close structural and functional homologues of Drosophila TRP. Although these channels can sometimes function as store-operated channels, in the majority of instances they function as channels more directly linked to phospholipase C activity. Three members of this family, TRPC3, 6 and 7, are activated by the phosphoinositide breakdown product, diacylglycerol. Two others, TRPC4 and 5, are also activated as a consequence of phospholipase C activity, although the precise substrate or product molecules involved are still unclear. Thus the TRPCs represent a family of ion channels that are directly activated by inositol lipid breakdown, confirming Bob Michell's original prediction 30 years ago.

Microbe Engineering of Guaia-6,10(14)-diene as a Building Block for the Semisynthetic Production of Plant-Derived (−)-Englerin A

2019 ◽  
Author(s):  
Thomas Siemon ◽  
Zhangqian Wang ◽  
Guangkai Bian ◽  
Tobias Seitz ◽  
Ziling Ye ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Saccharomyces Cerevisiae ◽  
Synthetic Biology ◽  
Chemical Synthesis ◽  
Building Block ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Economical Method ◽  
Englerin A ◽  
Transient Receptor

Herein, we report the semisynthetic production of the potent transient receptor potential canonical (TRPC) channel agonist (−)-englerin A (EA), using guaia-6,10(14)-diene as the starting material. Guaia-6,10(14)-diene was systematically engineered in Escherichia coli and Saccharomyces cerevisiae using the CRISPR/Cas9 system and produced with high titers. This provided us the opportunity to execute a concise chemical synthesis of EA and the two related guaianes (−)-oxyphyllol and (+)-orientalol E. The potentially scalable approach combines the advantages of synthetic biology and chemical synthesis and provides an efficient and economical method for producing EA as well as its analogs.

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