{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T14:17:14Z","timestamp":1778768234064,"version":"3.51.4"},"reference-count":27,"publisher":"SAGE Publications","issue":"7","license":[{"start":{"date-parts":[[2012,4,25]],"date-time":"2012-04-25T00:00:00Z","timestamp":1335312000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Dent Res"],"published-print":{"date-parts":[[2012,7]]},"abstract":"<jats:p>Amphotericin B, an antifungal drug used to treat candidiasis, has been reported to induce pro-inflammatory cytokine production in cultured cells. This study investigated the effects of amphotericin B on pro-inflammatory cytokine production in response to lipid A, the bioactive component of lipopolysaccharide (LPS) in the cell walls of Gram-negative bacteria. Amphotericin B alone elicited a slight increase in interleukin (IL)-6 and IL-8 production by human gingival fibroblasts. However, amphotericin B synergistically up-regulated lipid A-induced production of IL-6 and IL-8. While amphotericin B minimally activated nuclear factor (NF)-\u03baB, it synergistically increased lipid A\u2013induced NF-\u03baB activation. Pre-treatment with methyl-\u03b2-cyclodextrin (M\u03b2CD), a cholesterol-binding agent, reduced IL-6 and IL-8 production in human gingival fibroblasts. Cholesterol-saturated M\u03b2CD also reversed cytokine production, suggesting that the synergistic production of cytokines by amphotericin B and lipid A is dependent on cholesterol-rich microdomains. Amphotericin B activated caspase-8. In addition, a caspase-8 inhibitor inhibited IL-6 production by amphotericin B and lipid A. This suggests that caspase-8 is required for the synergistic production of IL-6 by amphotericin B and lipid A. Collectively, our results suggest that periodontal treatment carried out before amphotericin B treatment may protect against lipid A-induced pro-inflammatory cytokine production.<\/jats:p>","DOI":"10.1177\/0022034512446486","type":"journal-article","created":{"date-parts":[[2012,4,26]],"date-time":"2012-04-26T21:00:16Z","timestamp":1335474016000},"page":"709-714","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":9,"title":["Amphotericin B Up-regulates Lipid A-induced IL-6 Production\n                    <i>via<\/i>\n                    Caspase-8"],"prefix":"10.1177","volume":"91","author":[{"given":"R.","family":"Tamai","sequence":"first","affiliation":[{"name":"Department of Oral Medical Science, Ohu University School of Dentistry, 31-1 Misumido, Tomitamachi, Koriyama, Fukushima 963-8611, 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