{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T04:43:36Z","timestamp":1791607416020,"version":"4.3.4"},"reference-count":45,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2022,12,20]],"date-time":"2022-12-20T00:00:00Z","timestamp":1671494400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100005047","name":"Natural Science Foundation of Liaoning Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005047","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Environmental Toxicology"],"published-print":{"date-parts":[[2023,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The pro\u2010inflammation M1 to anti\u2010inflammation M2 macrophage ratio contribute to the severity of lipopolysaccharide (LPS)\u2010induced acute lung injury (ALI). JMJD3 aggravates the inflammatory reaction through affecting epigenetic modification and macrophage's phenotype to deteriorate ALI. To explore the mechanism underlying the upregulation of the macrophage M1\/M2 ratio through JMJD3, we developed an ALI mouse model using intratracheal LPS, LPS\u2010stimulated RAW 264.7 cells, and inhibited JMJD3 using GSK\u2010J4. H3K27me3 and H3K4me3 were investigated as JMJD3\u2010mediated epigenetic alteration sites in vivo and in vitro. C\/EBP\u03b2 and KDM5A were validated as linking factors between H3K27 and H3K4. IL4i1 was investigated as a JMJD3\u2010mediated targeted gene to regulate the macrophage M1\/M2 ratio. Chromatin immunoprecipitation was used to evaluate the relationship between H3K27me3 and\n                    <jats:italic>C\/ebp\u03b2<\/jats:italic>\n                    , C\/EBP\u03b2 and\n                    <jats:italic>Kdm5a<\/jats:italic>\n                    , H3K4me3 and\n                    <jats:italic>Il4i1<\/jats:italic>\n                    . Inhibiting JMJD3 with GSK\u2010J4 can relieve inflammation and pathological performance in ALI. JMJD3 can reduce IL4i1 expression to increase the macrophage M1\/M2 ratio and aggravated ALI which process was mediated via JMJD3\u2010indcued H3K27me3 and H3K4me3 demethylation, latter H3K4me3 demethylation inhibited IL4i1 transcription. Inhibiting JMJD3 with GSK\u2010J4 can increase IL4i1 expression, subsequently decreasing the expressions of M1 and increasing of M2 in vivo. The over\u2010expression IL4i1 in LPS\u2010stimulated macrophage or inhibiting JMJD3 with GSK\u2010J4 can both reverse the increase of the macrophage M1\/M2 ratio in vitro. C\/EBP\u03b2 and KDM5A were upregulated by LPS simulation, which linked JMJD3\u2010induced H3K27\u2010H3K4 demethylation. JMJD3 inhibited IL4i1 to increase the macrophage M1\/M2 phenotype ratio and aggravate LPS\u2010induced ALI. Using GSK\u2010J4 to inhibit JMJD3 may facilitate the treatment of LPS\u2010induced ALI.\n                  <\/jats:p>","DOI":"10.1002\/tox.23725","type":"journal-article","created":{"date-parts":[[2022,12,20]],"date-time":"2022-12-20T07:44:39Z","timestamp":1671522279000},"page":"754-769","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["<scp>JMJD3<\/scp>\n                    downregulates\n                    <scp>IL4i1<\/scp>\n                    aggravating lipopolysaccharide\u2010induced acute lung injury via\n                    <scp>H3K27<\/scp>\n                    and\n                    <scp>H3K4<\/scp>\n                    demethylation"],"prefix":"10.1002","volume":"38","author":[{"given":"Yizhuo","family":"Gao","sequence":"first","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine Shengjing Hospital of China Medical University  Shenyang 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