{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T18:27:24Z","timestamp":1784917644830,"version":"3.55.0"},"reference-count":50,"publisher":"Bioscientifica","issue":"2","content-domain":{"domain":["jme.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2016,8]]},"abstract":"<jats:p>\n                    The vitamin D metabolite 24,25-dihydroxyvitamin D\n                    <jats:sub>3<\/jats:sub>\n                    (24, 25[OH]\n                    <jats:sub>2<\/jats:sub>\n                    D\n                    <jats:sub>3<\/jats:sub>\n                    ) was shown to induce nongenomic signaling pathways in resting zone chondrocytes and other cells involved in bone remodeling. Recently, our laboratory demonstrated that 24,25-[OH]\n                    <jats:sub>2<\/jats:sub>\n                    D\n                    <jats:sub>3<\/jats:sub>\n                    but not 25-hydroxyvitamin D\n                    <jats:sub>3<\/jats:sub>\n                    , suppresses apolipoprotein A-I (apo A-I) gene expression and high-density lipoprotein (HDL) secretion in hepatocytes. Since 24,25-[OH]\n                    <jats:sub>2<\/jats:sub>\n                    D\n                    <jats:sub>3<\/jats:sub>\n                    has low affinity for the vitamin D receptor (VDR) and little is known with regard to how 24,25-[OH]\n                    <jats:sub>2<\/jats:sub>\n                    D\n                    <jats:sub>3<\/jats:sub>\n                    modulates nongenomic signaling in hepatocytes, we investigated the capacity of 24,25-[OH]\n                    <jats:sub>2<\/jats:sub>\n                    D\n                    <jats:sub>3<\/jats:sub>\n                    to activate various signaling pathways relevant to apo A-I synthesis in HepG2 cells. Treatment with 24,25-[OH]\n                    <jats:sub>2<\/jats:sub>\n                    D\n                    <jats:sub>3<\/jats:sub>\n                    resulted in decreased peroxisome proliferator-activated receptor alpha (PPAR\u03b1) expression and retinoid-X-receptor alpha (RXR\u03b1) expression. Similarly, treatment of hepatocytes with 50 nM 24,25-[OH]\n                    <jats:sub>2<\/jats:sub>\n                    D\n                    <jats:sub>3<\/jats:sub>\n                    for 1\u20133 h induced PKC\u03b1 activation as well as c-\n                    <jats:italic>jun<\/jats:italic>\n                    -N-terminal kinase 1 (JNK1) activity and extracellular-regulated kinase 1\/2 (ERK1\/2) activity. These changes in kinase activity correlated with changes in c-\n                    <jats:italic>jun<\/jats:italic>\n                    phosphorylation, an increase in AP-1-dependent transcriptional activity, as well as repression of apo A-I promoter activity. Furthermore, treatment with 24,25-[OH]\n                    <jats:sub>2<\/jats:sub>\n                    D\n                    <jats:sub>3<\/jats:sub>\n                    increased IL-1\u03b2, IL-6, and IL-8 expression by HepG2 cells. These observations suggest that 24,25-[OH]\n                    <jats:sub>2<\/jats:sub>\n                    D\n                    <jats:sub>3<\/jats:sub>\n                    elicits several novel rapid nongenomic-mediated pro-inflammatory protein kinases targeting AP1 activity, increasing pro-inflammatory cytokine expression, potentially impacting lipid metabolism and hepatic function.\n                  <\/jats:p>","DOI":"10.1530\/jme-16-0009","type":"journal-article","created":{"date-parts":[[2016,5,27]],"date-time":"2016-05-27T21:58:49Z","timestamp":1464386329000},"page":"87-96","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":9,"title":["Pro-inflammatory signaling by 24,25-dihydroxyvitamin D3 in HepG2 cells"],"prefix":"10.1530","volume":"57","author":[{"given":"Kent","family":"Wehmeier","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luisa 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