{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:05:37Z","timestamp":1792789537239,"version":"4.5.0"},"reference-count":156,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,12,26]],"date-time":"2021-12-26T00:00:00Z","timestamp":1640476800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008402","name":"Chengdu University of Traditional Chinese Medicine","doi-asserted-by":"publisher","award":["CZYHW1901"],"award-info":[{"award-number":["CZYHW1901"]}],"id":[{"id":"10.13039\/501100008402","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Sichuan Science and Technology Program","award":["2019YFH0108"],"award-info":[{"award-number":["2019YFH0108"]}]},{"DOI":"10.13039\/501100001602","name":"Science Foundation Ireland","doi-asserted-by":"publisher","award":["17\/CDA\/4708"],"award-info":[{"award-number":["17\/CDA\/4708"]}],"id":[{"id":"10.13039\/501100001602","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Macrophages are mononuclear phagocytes which derive either from blood-borne monocytes or reside as resident macrophages in peripheral (Kupffer cells of the liver, marginal zone macrophages of the spleen, alveolar macrophages of the lung) and central tissue (microglia). They occur as M1 (pro-inflammatory; classic) or M2 (anti-inflammatory; alternatively activated) phenotypes. Macrophages possess P2X7 receptors (Rs) which respond to high concentrations of extracellular ATP under pathological conditions by allowing the non-selective fluxes of cations (Na+, Ca2+, K+). Activation of P2X7Rs by still higher concentrations of ATP, especially after repetitive agonist application, leads to the opening of membrane pores permeable to ~900 Da molecules. For this effect an interaction of the P2X7R with a range of other membrane channels (e.g., P2X4R, transient receptor potential A1 [TRPA1], pannexin-1 hemichannel, ANO6 chloride channel) is required. Macrophage-localized P2X7Rs have to be co-activated with the lipopolysaccharide-sensitive toll-like receptor 4 (TLR4) in order to induce the formation of the inflammasome 3 (NLRP3), which then activates the pro-interleukin-1\u03b2 (pro-IL-1\u03b2)-degrading caspase-1 to lead to IL-1\u03b2 release. Moreover, inflammatory diseases (e.g., rheumatoid arthritis, Crohn\u2019s disease, sepsis, etc.) are generated downstream of the P2X7R-induced upregulation of intracellular second messengers (e.g., phospholipase A2, p38 mitogen-activated kinase, and rho G proteins). In conclusion, P2X7Rs at macrophages appear to be important targets to preserve immune homeostasis with possible therapeutic consequences.<\/jats:p>","DOI":"10.3390\/ijms23010232","type":"journal-article","created":{"date-parts":[[2021,12,27]],"date-time":"2021-12-27T01:00:54Z","timestamp":1640566854000},"page":"232","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":84,"title":["Inherent P2X7 Receptors Regulate Macrophage Functions during Inflammatory Diseases"],"prefix":"10.3390","volume":"23","author":[{"given":"Wenjing","family":"Ren","sequence":"first","affiliation":[{"name":"International Collaborative Centre on Big Science Plan for Purinergic Signalling, Chengdu University of TCM, Chengdu 610075, China"},{"name":"School of Acupunct3ure and Tuina, Chengdu University of TCM, Chengdu 610075, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrizia","family":"Rubini","sequence":"additional","affiliation":[{"name":"International Collaborative Centre on Big Science Plan for Purinergic Signalling, Chengdu University of TCM, Chengdu 610075, China"},{"name":"School of Acupunct3ure and Tuina, Chengdu University of TCM, Chengdu 610075, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2543-066X","authenticated-orcid":false,"given":"Yong","family":"Tang","sequence":"additional","affiliation":[{"name":"International Collaborative Centre on Big Science Plan for Purinergic Signalling, Chengdu University of TCM, Chengdu 610075, China"},{"name":"School of Acupunct3ure and Tuina, Chengdu University of TCM, Chengdu 610075, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9137-0637","authenticated-orcid":false,"given":"Tobias","family":"Engel","sequence":"additional","affiliation":[{"name":"Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, University of Medicine and Health Sciences, D02 YN77 Dublin, Ireland"},{"name":"FutureNeuro, SFI Research Centre for Chronic and Rare Neurological Diseases, RCSI University of Medicine and Health Sciences, D02 YN77 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0484-9389","authenticated-orcid":false,"given":"Peter","family":"Illes","sequence":"additional","affiliation":[{"name":"International Collaborative Centre on Big Science Plan for Purinergic Signalling, Chengdu University of TCM, Chengdu 610075, China"},{"name":"School of Acupunct3ure and Tuina, Chengdu University of TCM, Chengdu 610075, China"},{"name":"Rudolf Boehm Institute for Pharmacology and Toxicology, University of Leipzig, 04107 Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,26]]},"reference":[{"key":"ref_1","first-page":"509","article-title":"Purinergic nerves","volume":"24","author":"Burnstock","year":"1972","journal-title":"Pharmacol. 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