{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T17:02:36Z","timestamp":1790182956838,"version":"4.1.0"},"reference-count":53,"publisher":"Wiley","issue":"19","license":[{"start":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T00:00:00Z","timestamp":1760313600000},"content-version":"vor","delay-in-days":12,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Septic shock is one of the leading causes of morbidity and mortality in hospital patients. The present study aimed to investigate the potential of transforming growth factor \u03b2 induced (TGFBI) in macrophage functions and progression of septic shock. Mice were treated with caecal ligation and puncture (CLP) to establish a septic shock model in\u00a0vivo. Histopathologic analysis was performed using haematoxylin and eosin (HE) staining. Gene expression was detected using reverse transcription\u2010quantitative PCR and Western blot. Cytokine release was detected using an enzyme\u2010linked immunosorbent assay. The enrichment of TGFBI was detected using chromatin immunoprecipitation assay. Cellular functions were detected using Cell Counting Kit\u20108, lactate dehydrogenase, flow cytometry, PI staining, and terminal deoxynucleotidyl transferase\u2010mediated dUTP nick end labelling staining assays. TGFBI was downregulated in septic shock patients and models. TGFBI overexpression suppressed the pyroptosis of macrophages by inhibiting the non\u2010canonical inflammasome, promoting the bacterial killing ability of macrophages. Wedelolactone\u2010mediated inhibition of pyroptosis alleviated sepsis\u2010induced multiple organ failure. Moreover, TGFBI inhibited M1 macrophage polarisation. Suppressor of variegation 3\u20139 homologue 2 (SUV39H2)\u2010mediated histone methylation of TGFBI, resulting in the downregulation of TGFBI. Signal transducer and activator of transcription 1 (Stat1) was identified as a new co\u2010activator of SUV39H2 to inhibit the transcription of TGFBI. However, inhibition of SUV39H2 and Stat1 upregulated TGFBI. Furthermore, Stat1 deficiency inhibited the pyroptosis of macrophages and alleviated sepsis\u2010induced multiple organ failure. In summary, our findings establish an immune checkpoint, whereby TGFBI, via inhibiting macrophage pyroptosis and M1 polarisation, suppresses the progression of septic shock.<\/jats:p>","DOI":"10.1111\/jcmm.70802","type":"journal-article","created":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T01:17:10Z","timestamp":1760404630000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["<scp>TGFBI<\/scp> Inhibits the Pyroptosis of Macrophages to Ameliorate Septic Shock"],"prefix":"10.1111","volume":"29","author":[{"given":"Suzhao","family":"Zou","sequence":"first","affiliation":[{"name":"Department of Critical Care Medicine First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine  Guiyang 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