title: Extracellular ATP mediates inflammatory responses in colitis via P2 × 7 receptor signaling.
abstract: Extracellular purinergic products, particularly ATP, have recently been implicated to regulate immune cell functions and contribute to aberrant inflammatory responses of immune diseases. However, regulation of immune responses of colitis by extracellular ATP and its main receptor, P2 × 7, remains to be elucidated. In the study, we induced murine colitis by feeding mice with 4% dextran sulfate sodium (DSS), and noted dramatically heightened extracellular ATP levels in colon tissues during the progression of experimental colitis. Blockade of ATP release by carbenoxolone (CBX) treatment, or promoting ATP degradation by ATP diphosphohydrolase (apyrase), decreased extracellular ATP levels in colon tissues, attenuated DSS-induced colitis, whereas inhibition of extracellular ATP degradation by sodium metatungstate (POM-1) exacerbated tissue damage in the mice with colitis. Moreover, treatment with inhibitor of P2 × 7 receptor, A438079, decreased NFκB activation and active caspase-1 expression in lamina propria immune cells, downregulated proinflammatory cytokine production in colon tissues, and attenuated murine colitis. Collectively, these data suggest extracellular ATP participates in regulation of inflammatory responses of experimental colitis, through P2 × 7 receptor and inflammasome and NFκB signaling, which provides potential alternatives to the current clinical approaches to suppress extracellular ATP-mediated immune responsiveness.
authors.affiliation: Department of Gastroenterology, the First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Wan
authors.affiliation: Department of surgery, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, Guangdong Province, China.
authors.forename: Xiaopeng
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Gastroenterology, the First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xiong
authors.affiliation: Department of Gastroenterology, the First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China.
authors.forename: Yuping
authors.initials: Y
authors.lastname: Ren
authors.affiliation: Department of Gastroenterology, the First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Gastroenterology, the First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China.
authors.forename: Nonghua
authors.initials: N
authors.lastname: Lu
authors.affiliation: Department of Pharmacy, the First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Gastroenterology, the First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China.
authors.forename: Aiping
authors.initials: A
authors.lastname: Bai
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D020170:Caspase 1 / Q000378:metabolism; D003092:Colitis / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D016264:Dextran Sulfate / Q000009:adverse effects; D004195:Disease Models, Animal; D005110:Extracellular Space / Q000378:metabolism; D005260:Female; D018836:Inflammation Mediators / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D058920:Purinergic P2X Receptor Antagonists / Q000494:pharmacology; D058486:Receptors, Purinergic P2X7 / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D016328:NF-kappa B; D058920:Purinergic P2X Receptor Antagonists; D058486:Receptors, Purinergic P2X7; D000255:Adenosine Triphosphate; D016264:Dextran Sulfate; D020170:Caspase 1