Overexpression of ATP-activated P2X7 receptors in the intestinal mucosa is implicated in the pathogenesis of Crohn's disease.


BACKGROUND:Extracellular nucleotides released in conditions of cell stress alert the immune system from tissue injury or inflammation. We hypothesized that the P2X7 receptor (P2X7-R) could regulate key elements in inflammatory bowel disease pathogenesis. METHODS:Colonoscopy samples obtained from patients with Crohn's disease (CD), ulcerative colitis, and controls were used to analyze P2X7-R expression by RT and real-time PCR, immunohistochemistry, and confocal microscopy. Inflammatory response was determined by the levels of cytokines by enzyme-linked immunosorbent assay in cultures of intestinal explants. Apoptosis was determined by the TUNEL assay. P2X7-R C57BL/6 mice were treated with trinitrobenzene sulfonic acid or dextran sulfate sodium (DSS) for inducing colitis. RESULTS:P2X7-R was expressed in higher levels in inflamed CD epithelium and lamina propria, where it colocalizes more with dendritic cells and macrophages. Basal levels of P2X7-R mRNA were higher in CD inflamed mucosa compared with noninflamed CD and controls and were upregulated after interferon-γ in controls. Apoptotic rates were higher in CD epithelium and lamina propria compared with ulcerative colitis and controls. Levels of tumor necrosis factor-α, interleukin (IL)-1β, and IL-17 were higher, whereas IL-10 was lower in CD compared with controls. Levels of tumor necrosis factor-α-α and interleukin-1β increased after adenosine-triphosphate and decreased after KN62 treatment in CD. P2X7-R animals did not develop trinitrobenzene sulfonic acid or DSS colitis. CONCLUSIONS:The upregulation of P2X7-R in CD inflamed mucosa is consistent with the involvement of purinoceptors in inflammation and apoptosis. These observations may implicate purinergic signaling in the pathogenesis of intestinal inflammation, and the P2X7-R may represent a novel therapeutic target in CD.


Inflamm Bowel Dis


Neves AR,Castelo-Branco MT,Figliuolo VR,Bernardazzi C,Buongusto F,Yoshimoto A,Nanini HF,Coutinho CM,Carneiro AJ,Coutinho-Silva R,de Souza HS




Has Abstract


2014-03-01 00:00:00












  • Use of Complementary and Alternative Medicine for Inflammatory Bowel Disease Is Associated with Worse Adherence to Conventional Therapy: The COMPLIANT Study.

    abstract:BACKGROUND:Complementary and alternative medicine (CAM) use is highly prevalent among inflammatory bowel disease (IBD patients). We assessed whether its use, both for IBD and for general health, influenced adherence to conventional medications. METHODS:We enrolled 392 IBD subjects in a prospective cohort study and cat...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章


    authors: Nguyen GC,Croitoru K,Silverberg MS,Steinhart AH,Weizman AV

    更新日期:2016-06-01 00:00:00

  • Biomarker-Based Models Outperform Patient-Reported Scores in Predicting Endoscopic Inflammatory Disease Activity.

    abstract:Background:The Crohn's Disease Activity Index (CDAI), a scoring index including patient-reported outcomes (PROs), has known limitations for measuring intestinal inflammatory disease burden. Noninvasive markers of inflammation could prove more accurate than PROs; thus, regulatory authorities are exploring the use of PRO...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章,多中心研究


    authors: Morris MW,Stewart SA,Heisler C,Sandborn WJ,Loftus EV,Zello GA,Fowler SA,Jones JL

    更新日期:2018-01-18 00:00:00

  • Distinct Anti-IFI16 and Anti-GP2 Antibodies in Inflammatory Bowel Disease and Their Variation with Infliximab Therapy.

    abstract:BACKGROUND:Inflammatory bowel disease (IBD) is characterized by a chronic inflammation of the gut, partly driven by defects in the expression and function of pattern recognition receptors, including the IFI16 protein. Because this protein is a target for autoantibodies and its aberrant expression was reported in coloni...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章


    authors: Caneparo V,Pastorelli L,Pisani LF,Bruni B,Prodam F,Boldorini R,Roggenbuck D,Vecchi M,Landolfo S,Gariglio M,De Andrea M

    更新日期:2016-12-01 00:00:00

  • Crohn's disease-associated Escherichia coli LF82 aggravates colitis in injured mouse colon via signaling by flagellin.

    abstract:BACKGROUND:Ileal lesions in Crohn's disease patients are colonized by pathogenic adherent-invasive Escherichia coli (AIEC) that harbor various virulence factors involved in adhesion to and invasion of intestinal epithelial cultured cells. We investigated in a mouse model of colonic inflammation the behavior of virulent...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章


    authors: Carvalho FA,Barnich N,Sauvanet P,Darcha C,Gelot A,Darfeuille-Michaud A

    更新日期:2008-08-01 00:00:00

  • Impact of Concomitant Endometriosis on Phenotype and Natural History of Inflammatory Bowel Disease.

    abstract:BACKGROUND:Inflammatory bowel disease (IBD) and endometriosis are immune-mediated chronic inflammatory disorders affecting young women. The clinical significance of concomitant endometriosis on the course of IBD has not been previously studied. The aim of this study was to determine whether women with concomitant endom...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章


    authors: Lee KK,Jharap B,Maser EA,Colombel JF

    更新日期:2016-01-01 00:00:00

  • Adjustment to inflammatory bowel disease: the relative influence of illness perceptions and coping.

    abstract:BACKGROUND:The Common Sense Model (CSM) of illness representations was used in the current study to examine the relative contribution of illness perceptions and coping strategies in explaining adjustment to inflammatory bowel disease (IBD). METHODS:Participants were 80 adults consecutively attending an outpatients' cl...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章


    authors: Dorrian A,Dempster M,Adair P

    更新日期:2009-01-01 00:00:00

  • Capsule Endoscopy, Magnetic Resonance Enterography, and Small Bowel Ultrasound for Evaluation of Postoperative Recurrence in Crohn's Disease: Systematic Review and Meta-Analysis.

    abstract:Background:Anastomotic recurrence is frequent in patients with Crohn's disease (CD) following ileocecal resection. The degree of endoscopic recurrence, quantified by the Rutgeerts score (RS), is correlated with the risk of clinical and surgical recurrence. Noninvasive modalities such as capsule endoscopy (CE), magnetic...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章,meta分析


    authors: Yung DE,Har-Noy O,Tham YS,Ben-Horin S,Eliakim R,Koulaouzidis A,Kopylov U

    更新日期:2017-12-19 00:00:00

  • IL-1 receptor-associated kinase M downregulates DSS-induced colitis.

    abstract:BACKGROUND:Ulcerative colitis is associated with increased colon permeability resulting in bacterial translocation into the lamina propria. We investigate the importance of the Toll-like receptor (TLR) regulating protein IL-1 receptor-associated kinase M (IRAK-M) using the erosive dextran sulfate sodium (DSS)-induced m...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章


    authors: Berglund M,Melgar S,Kobayashi KS,Flavell RA,Hörnquist EH,Hultgren OH

    更新日期:2010-10-01 00:00:00

  • Fecal calprotectin levels and serological responses to microbial antigens among children and adolescents with inflammatory bowel disease.

    abstract:BACKGROUND:Noninvasive, sensitive, and specific tools for early identification of chronic inflammatory bowel disease (IBD) are needed for clinical practice. The aim was to identify new noninvasive test combinations for characterization of IBD in children and adolescents by comparing serological responses to microbial a...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章


    authors: Ashorn S,Honkanen T,Kolho KL,Ashorn M,Välineva T,Wei B,Braun J,Rantala I,Luukkaala T,Iltanen S

    更新日期:2009-02-01 00:00:00

  • Acute pancreatitis in patients with Crohn's disease: clinical features and outcomes.

    abstract:BACKGROUND:Acute pancreatitis has occasionally been associated with Crohn's disease (CD), but whether a causal association exists remains unclear. We sought to determine the frequency of etiologies in a consecutive series of patients with CD with acute pancreatitis. METHODS:A centralized diagnostic index was used to i...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章


    authors: Moolsintong P,Loftus EV Jr,Chari ST,Egan LJ,Tremaine WJ,Sandborn WJ

    更新日期:2005-12-01 00:00:00

  • Low-dose oral ferrous fumarate aggravated intestinal inflammation in rats with DSS-induced colitis.

    abstract:BACKGROUND:Oral ferrous iron therapy may reinforce intestinal inflammation. One possible mechanism is by catalyzing the production of reactive oxygen species. We studied the effects of low-dose oral ferrous fumarate on intestinal inflammation and plasma redox status in dextran sulfate sodium (DSS)-induced colitis in ra...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章


    authors: Erichsen K,Milde AM,Arslan G,Helgeland L,Gudbrandsen OA,Ulvik RJ,Berge RK,Hausken T,Berstad A

    更新日期:2005-08-01 00:00:00

  • Homing imprinting and immunomodulation in the gut: role of dendritic cells and retinoids.

    abstract::Lymphocyte migration is at the heart of chronic inflammatory ailments, including inflammatory bowel disease (IBD). Whereas naïve lymphocytes migrate to all secondary lymphoid organs, they are mostly excluded from nonlymphoid peripheral tissues. Upon activation, lymphocytes change their pattern of adhesion receptors an...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章,评审


    authors: Mora JR

    更新日期:2008-02-01 00:00:00

  • Galectin-2 and -4, but not galectin-1, promote intestinal epithelial wound healing in vitro through a TGF-beta-independent mechanism.

    abstract:BACKGROUND:Inflammatory bowel diseases (IBDs) are characterized by various degrees of mucosal surface damage and subsequent impairment of the intestinal barrier function. Resealing of the epithelial barrier requires intestinal cell migration and proliferation. Galectins are increasingly recognized as novel regulators o...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章


    authors: Paclik D,Lohse K,Wiedenmann B,Dignass AU,Sturm A

    更新日期:2008-10-01 00:00:00

  • Effect of 2 psychotherapies on depression and disease activity in pediatric Crohn's disease.

    abstract:BACKGROUND:Crohn's disease (CD) is associated with depression. It is unclear if psychosocial interventions offer benefit for depressive symptoms during active CD. In this secondary analysis of a larger study of treating depression in pediatric inflammatory bowel disease, we assessed whether cognitive behavioral therapy...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章,随机对照试验


    authors: Szigethy E,Youk AO,Gonzalez-Heydrich J,Bujoreanu SI,Weisz J,Fairclough D,Ducharme P,Jones N,Lotrich F,Keljo D,Srinath A,Bousvaros A,Kupfer D,DeMaso DR

    更新日期:2015-06-01 00:00:00

  • The Use of Cannabinoids in Colitis: A Systematic Review and Meta-Analysis.

    abstract:Background:Clinical trials investigating the use of cannabinoid drugs for the treatment of intestinal inflammation are anticipated secondary to preclinical literature demonstrating efficacy in reducing inflammation. Methods:We systematically reviewed publications on the benefit of drugs targeting the endo-cannabinoid ...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章,meta分析


    authors: Couch DG,Maudslay H,Doleman B,Lund JN,O'Sullivan SE

    更新日期:2018-03-19 00:00:00

  • VSL#3 Probiotic Stimulates T-cell Protein Tyrosine Phosphatase-mediated Recovery of IFN-γ-induced Intestinal Epithelial Barrier Defects.

    abstract:BACKGROUND:VSL#3 is a probiotic compound that has been used in the treatment of inflammatory bowel disease. T-cell protein tyrosine phosphatase (TCPTP) is the protein product of the inflammatory bowel disease candidate gene, PTPN2, and we have previously shown that it protects epithelial barrier function. The aim of th...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章


    authors: Krishnan M,Penrose HM,Shah NN,Marchelletta RR,McCole DF

    更新日期:2016-12-01 00:00:00

  • Diagnostic Accuracy of Blood-Based Tests and Histopathology for Cytomegalovirus Reactivation in Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis.

    abstract:BACKGROUND:It is unclear if traditional histopathology and noninvasive blood-based tests are sufficiently accurate to detect cytomegalovirus (CMV) reactivation in inflammatory bowel disease. Therefore, we assessed the diagnostic accuracy of these tests compared with immunohistochemistry (IHC) and tissue polymerase chai...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章,meta分析,评审


    authors: Tandon P,James P,Cordeiro E,Mallick R,Shukla T,McCurdy JD

    更新日期:2017-04-01 00:00:00

  • Association of Biomarker Cutoffs and Endoscopic Outcomes in Crohn's Disease: A Post Hoc Analysis From the CALM Study.

    abstract:BACKGROUND:CALM was a randomized phase 3 trial in patients with Crohn's disease (CD) that demonstrated improved endoscopic outcomes when treatment was escalated based on cutoffs for inflammatory biomarkers, fecal calprotectin (FC), C-reactive protein (CRP), and CD Activity Index (CDAI) remission vs CDAI response alone....

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章


    authors: Reinisch W,Panaccione R,Bossuyt P,Baert F,Armuzzi A,Hébuterne X,Travis S,Danese S,Sandborn WJ,Schreiber S,Berg S,Zhou Q,Kligys K,Neimark E,Suleiman AA,D'Haens G,Colombel JF

    更新日期:2020-09-18 00:00:00

  • Fecal excretion of deoxyribonucleic acid in long-term follow-up of patients with inactive ulcerative colitis.

    abstract:BACKGROUND:We have developed a technique for measuring fecal excretion of human DNA by assuming that luminal desquamation of epithelial and inflammatory cells increases in damaged colonic mucosa. However, the clinical usefulness of this technique in the follow-up of patients with ulcerative colitis has not been establi...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章


    authors: Casellas F,Borruel N,Antolín M,Varela E,Torrejón A,Armadans L,Guarner F,Malagelada JR

    更新日期:2007-04-01 00:00:00

  • Factors Associated with Discontinuation of Anti-TNF Inhibitors Among Persons with IBD: A Population-Based Analysis.

    abstract:INTRODUCTION:Antitumor necrosis factor (anti-TNF) medications are known to be highly efficacious in persons with moderate-to-severe inflammatory bowel disease (IBD). There is a paucity of data from population-based sources to elucidate persistence with these medications in the general population of IBD. Discontinuation...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章


    authors: Targownik LE,Tennakoon A,Leung S,Lix LM,Nugent Z,Singh H,Bernstein CN

    更新日期:2017-03-01 00:00:00

  • Phenotype classification in IBD: Is there an impact on therapy?

    abstract::This review summarizes the current phenotypic classifications of inflammatory bowel disease (IBD) and outlines their implications for diagnosis, therapy, prognosis, clinical trial design, and genotype-phenotype correlations. ...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章


    authors: Walfish A,Sachar D

    更新日期:2007-12-01 00:00:00

  • Ulcerative colitis and clinical course: results of a 5-year population-based follow-up study (the IBSEN study).

    abstract:BACKGROUND:The majority of studies concerning the clinical course and prognosis in ulcerative colitis (UC) are old, retrospective in design, or hospital based. We aimed to identify clinical course and prognosis in a prospective, population-based follow-up study MATERIALS AND METHODS:Patients diagnosed with inflammator...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章


    authors: Henriksen M,Jahnsen J,Lygren I,Sauar J,Kjellevold Ø,Schulz T,Vatn MH,Moum B,IBSEN Study Group.

    更新日期:2006-07-01 00:00:00

  • Smoking cessation alters intestinal microbiota: insights from quantitative investigations on human fecal samples using FISH.

    abstract:BACKGROUND:There has been a dramatic increase in investigations on the potential mechanistic role of the intestinal microbiota in various diseases and factors modulating intestinal microbial composition. We recently reported on intestinal microbial shifts after smoking cessation in humans. In this study, we aimed to co...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章


    authors: Biedermann L,Brülisauer K,Zeitz J,Frei P,Scharl M,Vavricka SR,Fried M,Loessner MJ,Rogler G,Schuppler M

    更新日期:2014-09-01 00:00:00

  • Independent Validation of a Self-Report Version of the IBD Disability Index (IBDDI) in a Population-Based Cohort of IBD Patients.

    abstract:Introduction:A new clinician-administered inflammatory bowel disease (IBD) Disability Index (IBDDI) was recently developed and validated among a population in France. We aimed to validate the IBDDI in a North American setting and adapt for use as a self-report tool. Methods:Persons 18-65 years old from the population-...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章


    authors: Shafer LA,Walker JR,Chhibba T,Ivekovic M,Singh H,Targownik LE,Peyrin-Biroulet L,Gower-Rousseau C,Sarter H,Bernstein CN

    更新日期:2018-03-19 00:00:00

  • The influence of depression on quality of life in patients with inflammatory bowel disease.

    abstract:BACKGROUND:Inflammatory bowel disease is a chronic inflammatory disorder of the gastrointestinal tract that significantly impacts the health-related quality of life (HR-QOL). A decreased HR-QOL has been demonstrated in patients with active disease compared with patients in remission. In this cross-sectional study, we e...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章


    authors: Zhang CK,Hewett J,Hemming J,Grant T,Zhao H,Abraham C,Oikonomou I,Kanakia M,Cho JH,Proctor DD

    更新日期:2013-07-01 00:00:00

  • A Population Pharmacokinetic and Exposure-Response Model of Golimumab for Targeting Endoscopic Remission in Patients With Ulcerative Colitis.

    abstract:BACKGROUND:Unlike other anti-tumor necrosis factor alpha antibodies, golimumab does not deliver on its promise of effectiveness for treating patients with ulcerative colitis. We investigated the value of therapeutic drug monitoring for optimizing golimumab therapy. METHODS:We analyzed the golimumab pharmacokinetics da...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章


    authors: Dreesen E,Kantasiripitak W,Detrez I,Stefanović S,Vermeire S,Ferrante M,Bouillon T,Drobne D,Gils A

    更新日期:2020-03-04 00:00:00

  • Etiopathogenesis of Nephrolithiasis in Ulcerative Colitis Patients with the Ileal Pouch Anal Anastomosis.

    abstract:BACKGROUND:Our previous study showed that nephrolithiasis is a common complication in ulcerative colitis patients after ileal pouch anal anastomosis (IPAA). However, the pathogenesis of nephrolithiasis in IPAA patients has not been studied. The aim of this study was to compare urine and serum metabolic compositions in ...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章


    authors: Arora Z,Mukewar S,Lopez R,Camino D,Shen B,Hall P

    更新日期:2017-05-01 00:00:00

  • Cell Trafficking Interference in Inflammatory Bowel Disease: Therapeutic Interventions Based on Basic Pathogenesis Concepts.

    abstract::After 20 years of successful targeting of pro-inflammatory cytokines for the treatment of IBD, an alternative therapeutic strategy has emerged, based on several decades of advances in understanding the pathogenesis of IBD. The targeting of molecules involved in leukocyte traffic has recently become a safe and effectiv...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章,评审


    authors: Pérez-Jeldres T,Tyler CJ,Boyer JD,Karuppuchamy T,Bamias G,Dulai PS,Boland BS,Sandborn WJ,Patel DR,Rivera-Nieves J

    更新日期:2019-01-10 00:00:00

  • Therapeutic effects of a new lymphocyte homing reagent FTY720 in interleukin-10 gene-deficient mice with colitis.

    abstract:BACKGROUND:FTY720 is a novel reagent that possesses potent immunosuppressive activity. The immunosuppression induced by FTY720 is mediated by completely different mechanisms from those of conventional immunosuppressants, that is, by altering the tissue distribution of lymphocytes rather than inhibiting activation. In t...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章


    authors: Mizushima T,Ito T,Kishi D,Kai Y,Tamagawa H,Nezu R,Kiyono H,Matsuda H

    更新日期:2004-05-01 00:00:00

  • Clostridium difficile Infection and Risk of Colectomy in Patients with Inflammatory Bowel Disease: A Bias-adjusted Meta-analysis.

    abstract:BACKGROUND:Clostridium difficile infection (CDI) is a common complication of inflammatory bowel diseases (IBDs) and is associated with worse outcome. Variable rates of colectomy have been reported among IBD complicated by CDI. We conducted a systematic review and meta-analysis of studies to assess the association betwe...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章,meta分析,评审


    authors: Chen Y,Furuya-Kanamori L,Doi SA,Ananthakrishnan AN,Kirk M

    更新日期:2017-02-01 00:00:00