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It sometimes results in septic shock. The present study aimed to identify quinolone antibiotics that can reduce tumor necrosis factor alpha (TNF\u03b1) production and to elucidate mechanisms underlying inhibition of TNF\u03b1 production. We identified quinolone antibiotics reduced TNF\u03b1 production in lipopolysaccharide (LPS)-stimulated THP-1 cells. Sitafloxacin (STFX) is a broad-spectrum antibiotic of the quinolone class. STFX effectively suppressed TNF\u03b1 production in LPS-stimulated THP-1 cells in a dose-dependent manner and increased extracellular signal-regulated kinase (ERK) phosphorylation. The percentage of intracellular TNF\u03b1 increased in LPS-stimulated cells with STFX compared with that in LPS-stimulated cells. TNF\u03b1 converting enzyme (TACE) released TNF\u03b1 from the cells, and STFX suppressed TACE phosphorylation and activity. To conclude, one of the mechanisms underlying inhibition of TNF\u03b1 production in LPS-stimulated THP-1 cells treated with STFX is the inhibition of TNF\u03b1 release from cells via the suppression of TACE phosphorylation and activity. STFX may kill bacteria and suppress inflammation. Therefore, it can be effective for sepsis treatment.<\/jats:p>","DOI":"10.1038\/s41598-021-03511-5","type":"journal-article","created":{"date-parts":[[2021,12,17]],"date-time":"2021-12-17T11:14:56Z","timestamp":1639739696000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Sitafloxacin reduces tumor necrosis factor alpha (TNF\u03b1) converting enzyme (TACE) phosphorylation and activity to inhibit TNF\u03b1 release from lipopolysaccharide-stimulated THP-1 cells"],"prefix":"10.1038","volume":"11","author":[{"given":"Ippei","family":"Sakamaki","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michika","family":"Fukushi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wakana","family":"Ohashi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yukie","family":"Tanaka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuhiro","family":"Itoh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kei","family":"Tomihara","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshihiro","family":"Yamamoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiromichi","family":"Iwasaki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,12,17]]},"reference":[{"key":"3511_CR1","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1001\/jama.2016.0287","volume":"315","author":"M Singer","year":"2016","unstructured":"Singer, M. et al. 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