P2X7 receptor blockade decreases inflammation,apoptosis,and enteric neuron loss during Clostridioides difficile toxin A-induced ileitis in mice

作     者：Ana A Q A Santos Deiziane V S Costa Danielle A Foschetti Antoniella S G Duarte Conceicao S Martins Pedro M G Soares Patricia Castelucci Gerly A C Brito 

作者机构：Department of MorphologySchool of MedicineFederal University of CearaFortaleza 60430-170CearaBrazil Department of Physiology and PharmacologySchool of MedicineFederal University of CearáFortaleza 60430-170CearaBrazil Department of Pathology and Legal MedicineSchool of MedicineFederal University of CearaFortaleza 60430-170CearaBrazil Department of Morphology(UFC)Federal University of CearaFortaleza 60430-170CearaBrazil Department of AnatomyInstitute of Biomedical SciencesUniversity of São PauloSao Paulo 05508-270Brazil Department of MorphologyFederal University of CearaFortaleza 60140-170CearaBrazil 

出 版 物：《World Journal of Gastroenterology》 (世界胃肠病学杂志（英文版）)

年 卷 期：2022年第28卷第30期

页      面：4075-4088页

核心收录：

学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

基　　金：Supported by PRONEX CNPq/FUNCAP,No.PR2-0101-00060.01.00/15 Sao Paulo Research Foundation(FAPESP),No.2014/25927-2 and No.2018/07862-1 

主　　题：Clostridioides difficile Clostridioides difficile toxin A P2X7 receptor Enteric nervous system Enteric neuron Enteric glia 

摘      要：Clostridioides difficile(***)is the most common pathogen causing health care-associated *** TcdA and TcdB have been shown to activate enteric neurons;however,what population of these cells is more profoundly influenced and the mechanism underlying these effects remain *** To characterize a specific population of TcdA-affected myenteric neurons and investigate the role of the P2X7 receptor in TcdA-induced ileal inflammation,cell death,and the changes in the enteric nervous system in *** Swiss mice were used to model TcdA-induced ileitis in ileal loops exposed to TcdA(50μg/Loop)for 4 *** investigate the role of the P2X7 receptor,Brilliant Blue G(50 mg/kg,i.p.),which is a nonspecific P2X7 receptor antagonist,or A438079(0.7μg/mouse,i.p.),which is a competitive P2X7 receptor antagonist,were injected one hour prior to TcdA *** samples were collected to analyze the expression of the P2X7 receptor(by quantitative real-time polymerase chain reaction and immunohistochemistry),the population of myenteric enteric neurons(immunofluorescence),histological damage,intestinal inflammation,cell death(terminal deoxynucleotidyltransferasemediated dUTP-biotin nick end labeling),neuronal loss,and S100B synthesis(immunohistochemistry).RESULTS TcdA upregulated(P0.05)the expression of the P2X7 receptor gene in the ileal tissues,increasing the level of this receptor in myenteric neurons compared to that in control *** with the control mice indicated that TcdA promoted(P0.05)the loss of myenteric calretinin+(Calr)and choline acetyltransferase+neurons and increased the number of nitrergic+and Calr+neurons expressing the P2X7 *** of the P2X7 receptor decreased TcdAinduced intestinal damage,cytokine release[interleukin(IL)-1β,IL-6,IL-8,and tumor necrosis factor-α],cell death,enteric neuron loss,and S100B synthesis in the mouse *** Our findings demonstrated that TcdA induced the upregulation of the P