{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T21:54:42Z","timestamp":1793224482256,"version":"4.5.0"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,2,10]],"date-time":"2025-02-10T00:00:00Z","timestamp":1739145600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005390","name":"Alfred \u00d6sterlunds Stiftelse","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005390","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003173","name":"Crafoordska Stiftelsen","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003173","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Serum Amyloid A (SAA) proteins are acute-phase reactants with critical roles in sterile and bacterial inflammation. Through\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    experiments, we demonstrate that SAA proteins amplify cytokine and chemokine responses during sterile inflammation and enhance bacterial clearance in infectious conditions. Mechanistically, SAA proteins augment NF-\u03baB signaling, driving pro and anti-inflammatory mediator production.\n                    <jats:italic>\n                      SAA\n                      <jats:sup>-\/-<\/jats:sup>\n                    <\/jats:italic>\n                    mice carrying a deletion of the\n                    <jats:italic>Saa1<\/jats:italic>\n                    ,\n                    <jats:italic>Saa2<\/jats:italic>\n                    ,\n                    <jats:italic>Saa3<\/jats:italic>\n                    , and\n                    <jats:italic>Saa4<\/jats:italic>\n                    serum amyloid A genes have better survival rates in sterile sepsis but are more prone to bacterial sepsis than their\n                    <jats:italic>\n                      SAA\n                      <jats:sup>+\/+<\/jats:sup>\n                    <\/jats:italic>\n                    counterparts, emphasizing their dual functionality in immune regulation. Overexpression of\n                    <jats:italic>Saa1<\/jats:italic>\n                    ,\n                    <jats:italic>Saa2<\/jats:italic>\n                    ,\n                    <jats:italic>Saa3<\/jats:italic>\n                    , and\n                    <jats:italic>Saa4<\/jats:italic>\n                    in macrophages enhances NF-\u03baB-mediated pro-inflammatory cytokine production and bacterial clearance during infection. Together, our results show that SAA proteins are key modulators of inflammation, with distinct mechanisms tailored to sterile and infectious contexts.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2025.1544085","type":"journal-article","created":{"date-parts":[[2025,2,10]],"date-time":"2025-02-10T01:50:37Z","timestamp":1739152237000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":26,"title":["Balancing inflammation: the specific roles of serum amyloid A proteins in sterile and infectious 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