Prophylactic Oral Administration of Magnesium Ameliorates Dextran Sulfate Sodium-Induced Colitis in Mice through a Decrease of Colonic Accumulation of P2X7 Receptor-Expressing Mast Cells

Ohbori, Kenshi; Fujiwara, Makiko; Ohishi, Akihiro; Nishida, Kazuhiro; Uozumi, Yoshinobu; Nagasawa, Kohei

doi:10.1248/bpb.b17-00143

Cited by 15 publications

(21 citation statements)

References 37 publications

(65 reference statements)

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“… 24 Preventive oral magnesium could ameliorate colitis by reducing the accumulation of P2X7R-expressing mast cells in the colon. 40 In addition to intestinal inflammation, studies have shown that ATP-driven mast cell activation by P2X7R is also a potential trigger for neuro-inflammation and pain sensitization in migraine. 25 Until now, the relationship between P2X7R in mast cells and inflammatory pain has not been clarified.…”

Section: Discussionmentioning

confidence: 99%

P2X7R in Mast Cells is a Potential Target for Salicylic Acid and Aspirin in Treatment of Inflammatory Pain

Jiang¹,

Ye²,

Du³

et al. 2021

JIR

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Background Mast cells are well known for their role in inflammatory pain. P2X7 receptor (P2X7R) has attracted much attention due to its prominent role in inflammatory diseases. Salicylates are commonly used anti-inflammatory and analgesic drugs. Until now, little has been known about whether P2X7R in mast cells is involved in inflammatory pain and whether it is a potential target for salicylates. Methods First, the expression of P2X receptors in mouse peritoneal mast cells was detected by using RT-PCR, immunofluorescence, calcium imaging and electrophysiological technique. In addition, the functions of P2X receptors, especially P2X7R, in mast cells were studied by using QPCR, ELISA and behavioral tests. Furthermore, P2X7R was used as a target to screen for some anti-inflammatory monomers that could inhibit its activity. At last, the effect of salicylic acid (SA) and aspirin (ASA) on the activity of P2X7R was studied by using calcium imaging, electrophysiological technique, ELISA, real-time PCR, behavioral tests, immunofluorescence and molecular docking. Results We found that P2X1, P2X3, P2X4 and P2X7 receptors were expressed in mouse peritoneal mast cells. The functions of different P2X receptors were various. Activation of P2X7R in mouse mast cells induced the release of inflammatory mediators, such as histamine, IL-1β, and CCL3. In addition, inflammation pain induced by high concentrations of ATP could be alleviated by P2X7R blockers or mast cell defects. Interestingly, SA or ASA could reduce high concentrations of ATP-induced inward current, P2X7R upregulation, mediators release, and inflammatory pain. SA or ASA also inhibited the inward current evoked by P2X7R agonist, BZATP. Molecular docking showed that SA or ASA had affinity for the cytoplasmic GDP-binding region of P2X7R. Conclusion P2X7R in mast cells was involved in inflammation pain by releasing inflammatory mediators, and P2X7R might be a potential target for SA and ASA analgesia.

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Section: Discussionmentioning

confidence: 99%

P2X7R in Mast Cells is a Potential Target for Salicylic Acid and Aspirin in Treatment of Inflammatory Pain

Jiang¹,

Ye²,

Du³

et al. 2021

JIR

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“…Furthermore, eATP/P2X7R-mediated activation of mast cells not only induces degranulation and inflammatory cytokines, but also chemokines and leukotriene B4 (LTB4) to recruit inflammatory cells (e.g., neutrophils) and subsequently exacerbate intestinal inflammation [18] (Figure 1). Therefore, targeting eATP-mediated mast-cell activation might be a promising novel strategy for the prevention and treatment of intestinal inflammation [70]. In another setting, eATP-P2X7R induced the death of regulatory T cells (Treg), which suppress colitis [63,71].…”

Section: Eatp As An Inflammatory Mediator In Intestinal Inflammationmentioning

confidence: 99%

ATP as a Pathophysiologic Mediator of Bacteria-Host Crosstalk in the Gastrointestinal Tract

Inami

Kiyono

Kurashima

2018

IJMS

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Extracellular nucleotides, such as adenosine triphosphate (ATP), are released from host cells including nerve termini, immune cells, injured or dead cells, and the commensal bacteria that reside in the gut lumen. Extracellular ATP interacts with the host through purinergic receptors, and promotes intercellular and bacteria-host communication to maintain the tissue homeostasis. However, the release of massive concentrations of ATP into extracellular compartments initiates acute and chronic inflammatory responses through the activation of immunocompetent cells (e.g., T cells, macrophages, and mast cells). In this review, we focus on the functions of ATP as a pathophysiologic mediator that is required for the induction and resolution of inflammation and inter-species communication.

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“…In the GI system, P2X7R expressed in different cell types has various actions under homeostatic and pathological conditions studied under different experimental models, e.g., colitis model ( Gulbransen et al, 2012 ; Kurashima et al, 2012 ; Antonioli et al, 2014 ; Marques et al, 2014 ; Neves et al, 2014 ; Hofman et al, 2015 ; Wan et al, 2016 ; Figliuolo et al, 2017 ; Hashimoto-Hill et al, 2017 ; Ohbori et al, 2017 ; Diezmos et al, 2018 ; Souza et al, 2020 ; Saber et al, 2021 ), sepsis model via caecal ligation and puncture (CLP) ( Wu et al, 2017 ; Alarcón-Vila et al, 2020 ), infection models ( Keating et al, 2011 ; Huang et al, 2017 ; Shimokawa et al, 2017 ; Liu et al, 2018 ; Quan et al, 2018 ; Stark et al, 2018 ) in both animal and human studies. There were also a few studies ( Bourzac et al, 2013 ; Proietti et al, 2014 ; Arguin et al, 2017 ; Perruzza et al, 2017 ; Perruzza et al, 2019 ; Proietti et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Understanding the Role of Purinergic P2X7 Receptors in the Gastrointestinal System: A Systematic Review

Cheng¹,

Zhang²,

Liu³

2021

Front. Pharmacol.

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Background: The role of purinergic P2X7 receptor (P2X7R) is of interest due to its involvement in inflammation and mediating immune cell responses. P2X7R is particularly implicated in the development of inflammatory bowel disease (IBD). However, the extent of the actions of P2X7R in the gastrointestinal (GI) system under physiological and pathophysiological conditions remains to be elucidated. This systematic review aimed to identify, summarize and evaluate the evidence for a critical role of P2X7R in the GI system.Methods: We searched PubMed, Embase and Scopus with search terms pertained to P2X7R in the GI system in disease or physiological state, including “P2X7 or P2X7 receptor or purinergic signaling” in combination with any of the terms “intestine or colon or gut or gastrointestinal,” “pathology or inflammation or disease or disorder,” and “physiology or expression.” Titles and abstracts were screened for potentially eligible full texts, and animal and human studies published in English were included in this study. Data were extracted from papers meeting inclusion criteria. Meta-analysis was not feasible given the study diversity.Results: There were 48 papers included in this review. We identified 14 experimental colitis models, three sepsis models and one ischemia-reperfusion injury model. Among them, 11 studies examined P2X7R in GI infections, six studies on immune cell regulation, four studies on GI inflammation, two studies on GI malignancies, three studies involving intestinal injury due to various causes, two studies on ATP-activated P2X7R in the GI system and two studies on metabolic regulation.Conclusion: Evidence supports P2X7R mediating inflammation and immune cell responses in GI inflammation, infections and injury due to IBD and other challenges to the intestinal wall. P2X7R inhibition by gene knockout or by application of P2X7R antagonists can reduce tissue damage by suppressing inflammation. P2X7R is also implicated in GI malignancies and glucose and lipid homeostasis. P2X7R blockade, however, did not always lead to beneficial outcomes in the various pathological models of study.

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Prophylactic Oral Administration of Magnesium Ameliorates Dextran Sulfate Sodium-Induced Colitis in Mice through a Decrease of Colonic Accumulation of P2X7 Receptor-Expressing Mast Cells

Cited by 15 publications

References 37 publications

P2X7R in Mast Cells is a Potential Target for Salicylic Acid and Aspirin in Treatment of Inflammatory Pain

P2X7R in Mast Cells is a Potential Target for Salicylic Acid and Aspirin in Treatment of Inflammatory Pain

ATP as a Pathophysiologic Mediator of Bacteria-Host Crosstalk in the Gastrointestinal Tract

Understanding the Role of Purinergic P2X7 Receptors in the Gastrointestinal System: A Systematic Review

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