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However, the function and mechanism of cGAS\u2013STING in SAP-induced lung injury (LI) remains unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Lipopolysaccharide (LPS) was combined with caerulein-induced SAP in wild type,\n                      <jats:italic>cGAS<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>\u2212\/\u2212<\/jats:italic>\n                      <\/jats:sup>\n                      and\n                      <jats:italic>sting<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>\u2212\/\u2212<\/jats:italic>\n                      <\/jats:sup>\n                      mice\n                      <jats:italic>.<\/jats:italic>\n                      Primary macrophages were extracted via bronchoalveolar lavage and peritoneal lavage. Ana-1 cells were pretreated with LPS and stimulated with nigericin sodium salt to induce pyroptosis in\u00a0vitro.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      SAP triggered NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome activation-mediated pyroptosis of alveolar and peritoneal macrophages in mouse model. Knockout of\n                      <jats:italic>cGAS<\/jats:italic>\n                      \/\n                      <jats:italic>STING<\/jats:italic>\n                      could ameliorate NLRP3 activation and macrophage pyroptosis. In addition, mitochondrial (mt)DNA released from damaged mitochondria further induced macrophage STING activation in a cGAS- and dose-dependent manner. Upregulated STING signal can promote NLRP3 inflammasome-mediated macrophage pyroptosis and increase serum interleukin (IL)-6, IL-1\u03b2, and tumor necrosis factor (TNF)-\u03b1 levels and, thus, exacerbate SAP-associated LI (SAP-ALI). Downstream molecules of STING, IRF7, and IRF3 connect the mtDNA\u2013cGAS\u2013STING axis and the NLRP3\u2013pyroptosis axis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Negative regulation of any molecule in the mtDNA\u2013cGAS\u2013STING\u2013IRF7\/IRF3 pathway can affect the activation of NLRP3 inflammasomes, thereby reducing macrophage pyroptosis and improving SAP-ALI in mouse model.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s11658-024-00575-9","type":"journal-article","created":{"date-parts":[[2024,4,26]],"date-time":"2024-04-26T23:41:27Z","timestamp":1714174887000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":89,"title":["Mitochondrial (mt)DNA\u2013cyclic GMP\u2013AMP synthase (cGAS)\u2013stimulator of interferon genes (STING) signaling promotes pyroptosis of macrophages via interferon regulatory factor (IRF)7\/IRF3 activation to aggravate lung injury during severe acute pancreatitis"],"prefix":"10.1186","volume":"29","author":[{"given":"Yiqiu","family":"Peng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxi","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingying","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingjuan","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruixia","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingyi","family":"Luan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongming","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenghong","family":"Yin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,4,27]]},"reference":[{"issue":"12","key":"575_CR1","doi-asserted-by":"publisher","first-page":"1251","DOI":"10.1007\/s40265-022-01766-4","volume":"82","author":"P Szatmary","year":"2022","unstructured":"Szatmary P, Grammatikopoulos T, Cai W, Huang W, Mukherjee R, Halloran C, et\u00a0al. 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