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The present study examined how DGK\u03b5 depletion affects lipopolysaccharide (LPS)\u2010mediated inflammatory responses at the cellular and organismal levels. In the early phase, DGK\u03b5\u2010deficient cells showed reduced phosphorylation levels of Akt and NF\u2010\u03baB p65 subunit. In the animal model of endotoxin shock, DGK\u03b5\u2010deficient mice showed full survival (100%) at 24\u2009h after LPS administration, compared to the wild\u2010type mice survival rate of 53%. In this setting, TNF\u2010\u03b1 and iNOS, the NF\u2010\u03baB\u2010inducible inflammatory genes, were downregulated in DGK\u03b5\u2010deficient liver. Furthermore, free radical\u2010mediated cytotoxicity as evaluated by 8\u2010OHdG staining was significantly lower in the liver. Results suggest that DGK\u03b5 depletion suppresses the NF\u2010\u03baB pathway, thereby conferring resistance to endotoxin shock in mice.<\/jats:p>\n                  <jats:p>\n                    <jats:boxed-text content-type=\"box\" position=\"anchor\">\n                      <jats:caption>\n                        <jats:title>Impact statement<\/jats:title>\n                      <\/jats:caption>\n                      <jats:p>We examined how DGK\u03b5 depletion affects LPS\u2010mediated inflammatory responses. At the cellular level, NF\u2010\u03baB signaling was attenuated in DGK\u03b5\u2010deficient cells. DGK\u03b5\u2010deficient mice were less vulnerable to endotoxin shock than the wild\u2010type. Our results suggest DGK\u03b5 depletion promotes suppression of the NF\u2010\u03baB pathway, thereby conferring resistance to endotoxin shock in mice.<\/jats:p>\n                    <\/jats:boxed-text>\n                  <\/jats:p>","DOI":"10.1002\/1873-3468.70164","type":"journal-article","created":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T09:01:19Z","timestamp":1757926879000},"page":"3629-3641","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Diacylglycerol kinase \u03b5 depletion suppresses\n                    <scp>LPS<\/scp>\n                    \u2010stimulated\n                    <scp>NF<\/scp>\n                    \u2010\n                    <scp>\u03baB<\/scp>\n                    activation and reduces free radical\u2010induced\n                    <scp>DNA<\/scp>\n                    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