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It has been suggested previously that purinergic P2X7 receptor signaling is critical for crystal-induced inflammasome activation and renal injury. Therefore, we investigated the role of the P2X7 receptor in response to crystal-induced cytokine release, inflammation, and kidney failure using <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic> models. Dendritic cells and macrophages derived from murine bone marrow and human peripheral blood mononucleated cells stimulated with calcium-oxalate crystals, monosodium urate crystals, or ATP lead to the robust release of interleukin-1beta (IL-1\u00df). Treatment with the P2X7 inhibitor A740003 or the depletion of ATP by apyrase selectively abrogated ATP-induced, but not oxalate and urate crystal-induced IL-1\u00df release. In line with this finding, dendritic cells derived from bone marrow (BMDCs) from <jats:italic>P2X7<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mice released reduced amounts of IL-1\u00df following stimulation with ATP, while oxalate and urate crystal-induced IL-1\u00df release was unaffected. In sharp contrast, BMDCs from <jats:italic>Casp1<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mice exhibited reduced IL-1\u00df release following either of the three stimulants. In addition, <jats:italic>P2X7<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mice demonstrated similar degrees of crystal deposition, tubular damage and inflammation when compared with WT mice. In line with these findings, increases in plasma creatinine were no different between WT and <jats:italic>P2X7<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mice. In contrast to previous reports, our results indicate that P2X7 receptor is not required for crystal-induced CKD and it is unlikely to be a suitable therapeutic target for crystal-induced progressive kidney disease.<\/jats:p>","DOI":"10.1038\/s41598-019-56560-2","type":"journal-article","created":{"date-parts":[[2019,12,27]],"date-time":"2019-12-27T11:02:42Z","timestamp":1577444562000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["P2X7 Receptor Stimulation Is Not Required for Oxalate Crystal-Induced Kidney Injury"],"prefix":"10.1038","volume":"9","author":[{"given":"Hannah L.","family":"Luz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Reichel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J.","family":"Unwin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9006-5112","authenticated-orcid":false,"given":"Kerim","family":"Mutig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9462-1681","authenticated-orcid":false,"given":"Ana C.","family":"Najenson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise M.","family":"Tonner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai-Uwe","family":"Eckardt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0614-9856","authenticated-orcid":false,"given":"Frederick W. 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