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Res."],"published-print":{"date-parts":[[2024,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>\n                      Cellular NAD\n                      <jats:sup>+<\/jats:sup>\n                      declines in inflammatory states associated with increased activity of the leukocyte-expressed NADase CD38. In this study, we tested the potential role of therapeutically targeting CD38 and NAD\n                      <jats:sup>+<\/jats:sup>\n                      in gout.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We studied cultured mouse wild type and CD38 knockout (KO) murine bone marrow derived macrophages (BMDMs) stimulated by monosodium urate (MSU) crystals and used the air pouch gouty inflammation model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      MSU crystals induced CD38 in BMDMs in vitro, associated with NAD\n                      <jats:sup>+<\/jats:sup>\n                      depletion, and IL-1\u03b2 and CXCL1 release, effects reversed by pharmacologic CD38 inhibitors (apigenin, 78c). Mouse air pouch inflammatory responses to MSU crystals were blunted by CD38 KO and apigenin. Pharmacologic CD38 inhibition suppressed MSU crystal-induced NLRP3 inflammasome activation and increased anti-inflammatory SIRT3\u2013SOD2 activity in macrophages. BMDM RNA-seq analysis of differentially expressed genes (DEGs) revealed CD38 to control multiple MSU crystal-modulated inflammation pathways. Top DEGs included the circadian rhythm modulator\n                      <jats:italic>GRP176<\/jats:italic>\n                      , and the metalloreductase\n                      <jats:italic>STEAP4<\/jats:italic>\n                      that mediates iron homeostasis, and promotes oxidative stress and NF-\u03baB activation when it is overexpressed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      CD38 and NAD\n                      <jats:sup>+<\/jats:sup>\n                      depletion are druggable targets controlling the MSU crystal- induced inflammation program. Targeting CD38 and NAD\n                      <jats:sup>+<\/jats:sup>\n                      are potentially novel selective molecular approaches to limit gouty arthritis.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00011-024-01863-y","type":"journal-article","created":{"date-parts":[[2024,3,16]],"date-time":"2024-03-16T16:01:24Z","timestamp":1710604884000},"page":"739-751","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["The NADase CD38 is a central regulator in gouty inflammation and a novel druggable therapeutic target"],"prefix":"10.1007","volume":"73","author":[{"given":"Paulo Gil","family":"Alabarse","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Oliveira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huaping","family":"Qin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiffany","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Migaud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Terkeltaub","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9611-8163","authenticated-orcid":false,"given":"Ru","family":"Liu-Bryan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,3,16]]},"reference":[{"key":"1863_CR1","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1186\/s12916-017-0922-5","volume":"15","author":"R Terkeltaub","year":"2017","unstructured":"Terkeltaub R. 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