P2X7 receptor antagonist recovers ileum myenteric neurons after experimental ulcerative colitis

Souza, Roberta de Castro; Evangelinellis, Mariá Munhoz; Mendes, Cristina Eusébio; Righetti, M.; Lourenço, Múcio Cevulla Silva; Castelucci, Patrícia

doi:10.4291/wjgp.v11.i4.84

Cited by 11 publications

(20 citation statements)

References 46 publications

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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%

“…Eleven experimental colitis models were undertaken in rats and/or mice ( Gulbransen et al, 2012 ; Antonioli et al, 2014 ; Marques et al, 2014 ; Hofman et al, 2015 ; Wan et al, 2016 ; Figliuolo et al, 2017 ; Hashimoto-Hill et al, 2017 ; Ohbori et al, 2017 ; Delvalle et al, 2018 ; Souza et al, 2020 ; Saber et al, 2021 ), one study involved human colonic tissue culture ( Diezmos et al, 2018 ), and two studies involved both mouse models and colonic tissues from IBD patients ( Gulbransen et al, 2012 ; Kurashima et al, 2012 ; Neves et al, 2014 ). To induce colitis, two studies used TNBS–25 mg in 1 ml of solution ( Marques et al, 2014 ), 30 mg/kg in 600 μl of 30% ethanol ( Souza et al, 2020 ). Two studies used TNBS and DSS–100 μl of 2.5% TNBS in 50% ethanol and 3.5% or 2.5% DSS in drinking water ad libitum ( Kurashima et al, 2012 ); 25 mg of TNBS in 0.1 ml solution and 5% DSS in drinking water ad libitum ( Neves et al, 2014 ).…”

Section: Discussionmentioning

confidence: 99%

“…administration of naïve CD4 + T cells (5 × 10 5 cells/mouse) ( Hashimoto-Hill et al, 2017 ). Twelve studies involved P2X7R antagonists ( Gulbransen 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 ; Ohbori et al, 2017 ; Delvalle et al, 2018 ; Diezmos et al, 2018 ; Souza et al, 2020 ; Saber et al, 2021 ), four studies involved P2X7R KO mice ( Neves et al, 2014 ; Hofman et al, 2015 ; Figliuolo et al, 2017 ; Hashimoto-Hill et al, 2017 ), two studies used anti-P2X7R antibodies ( Kurashima et al, 2012 ; Neves et al, 2014 ), and one study used reconstituted P2X7R deficient mast cells ( Kurashima et al, 2012 ).…”

Section: Discussionmentioning

confidence: 99%

“…In the studies involving P2X7R antagonists, Marques et al (2014) showed that prophylactic systemic administration of P2X7R antagonist, e.g., Brilliant Blue G (BBG, 40 mg/kg) or A740003 (16 mg/kg) 24 h prior to TNBS injection, was highly efficacious in attenuating colitis-induced tissue damage, apoptosis and inflammatory responses. Souza et al (2020) described improvements in clinical signs of colitis in the BBG-treated group (50 mg/kg administered 1 h following TNBS injection) ( Souza et al, 2020 ). Ohbori et al (2017) also found that per oral (p.o.)…”

Section: Discussionmentioning

confidence: 99%

“…This was the only paper to study chemically-induced colitis with colitis-associated cancer, which was induced using azoymethane over a duration of 2 months. This was significantly longer than other studies which lasted from 1 ( Souza et al, 2020 ) to 11 days ( Ohbori et al, 2017 ), allowing Hofman et al (2015) to examine the longer term effects of P2X7R blockade in chemically-induced colitis. The long-term implications seen here are important to consider with the growing interest in using P2X7R blockade to treat IBD.…”

Section: Discussionmentioning

confidence: 99%

See 4 more Smart Citations

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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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 3 more Smart Citations

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

Cheng¹,

Zhang²,

Liu³

2021

Front. Pharmacol.

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In focus in HCB

Taatjes

Roth

2022

Histochem Cell Biol

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The Editorial of the first issue of Histochemistry and Cell Biology in 2022 starts with "Most popular articles published in HCB in 2019" and continues to highlight one Review about dynamic changes of histone methylation in mammalian oocytes and early embryos and three Original Articles reporting (1) that fat causes necrosis and inflammation in human steatotic liver, (2) the effect of a P2X7 receptor antagonist in a rat model of ulcerative colitis, and (3) NANOS3 downregulation in Down syndrome hiPSCs. We wish you good reading!

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Effects of experimental ulcerative colitis on myenteric neurons in P2X7-knockout mice

Machado¹,

Souza²,

Figliuolo³

et al. 2023

Histochem Cell Biol

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The objective was to study the distal colon myenteric plexus and enteric glial cells (EGCs) in P2X7 receptor-de cient (P2X7-/-) animals after experimental ulcerative colitis on. 2, 4, 6-trinitrobenzene sulfonic acid (TNBS) was injected into distal colon of C57BL/6 (WT) and P2X7 receptor gene-de cient (P2X7-/-, KO) animals. Distal colon tissues were analysed 24 h and 4 d after administration. Double immuno uorescence was used for analyses and histology was used for morphological analysis. Quantitative analysis demonstrated 13.9% and 7.1% decreases in the number/ganglia of P2X7 receptor-immunoreactive (ir) in the 24 h-WT/colitis group and 4 d-WT/colitis, respectively. There was no reduction in the number per ganglia of neuronal nitric oxide synthase (nNOS)-ir, choline acetyltransferase (ChAT)-ir and PGP9.5 (pan neuronal)-ir neurons in the 4 d-KO/colitis group. There was a reduction by 19.3% in the number of glial brillary acidic protein (GFAP, EGC)-ir in the 24 h-WT/colitis group and a 19% increase in the number of these cells in the 4 d-WT/colitis group. There were no pro le area changes in neurons in the 24 h groups. In the 4 d-WT/colitis and 4 d-KO/colitis groups, there was an increase in the pro le neuronal area of nNOS, ChAT and PGP9.5. Histological analysis showed hyperaemia, oedema or cellular in ltration in the 24 h-WT/colitis groups and 4 d-WT/colitis groups. The 4 d-KO/colitis groups showed no histological changes.

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P2X7 receptor antagonist recovers ileum myenteric neurons after experimental ulcerative colitis

Cited by 11 publications

References 46 publications

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

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

In focus in HCB

Effects of experimental ulcerative colitis on myenteric neurons in P2X7-knockout mice

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