{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T15:10:45Z","timestamp":1788793845771,"version":"build-2803163510"},"reference-count":54,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science KAKENHI","doi-asserted-by":"crossref","award":["16K08630"],"award-info":[{"award-number":["16K08630"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science KAKENHI","doi-asserted-by":"crossref","award":["19K07405"],"award-info":[{"award-number":["19K07405"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science KAKENHI","doi-asserted-by":"crossref","award":["22K06914"],"award-info":[{"award-number":["22K06914"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Polymyxins are cyclic cationic lipopeptide antibiotics that disrupt both the outer and inner membranes of Gram-negative bacteria. They also bind to bacterial lipopolysaccharides (LPSs), thereby inhibiting LPS recognition by Toll-like receptor 4 (TLR4) and preventing macrophage activation. However, the immunomodulatory effects of polymyxin B during infection, in which multiple host- and bacteria-derived factors coexist, remain unclear. In this study, we examined the impact of polymyxin B, a representative polymyxin antibiotic, on mouse macrophage responses in the presence of interferon \u03b3 (IFN-\u03b3), with or without LPS stimulation. Polymyxin B induced nitric oxide (NO) production when macrophages were exposed to high concentrations of IFN-\u03b3. In the presence of lower concentrations of IFN-\u03b3, polymyxin B alone cannot induce NO production, but together with LPS can cause the induction of NO production. These NO productions were not largely affected by TLR4 deficiency but were attenuated when TLR2 was deficient. Furthermore, polymyxin B\u2013immobilized agarose beads precipitated TLR2 from cell extracts, indicating an association between polymyxin B and TLR2. This association was not inhibited by LPS, although polymyxin B and LPS synergistically induced NO production. Collectively, these findings demonstrate that polymyxin B (together with LPS) associates with TLR2 and functions as a TLR2 agonist, suggesting that polymyxin B preparations can induce macrophage activation under conditions in which IFN-\u03b3 and LPS are present.<\/jats:p>","DOI":"10.1093\/jimmun\/vkag193","type":"journal-article","created":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T05:22:46Z","timestamp":1784265766000},"source":"Crossref","is-referenced-by-count":0,"title":["Hidden effects of polymyxin B: Its role in activating TLR2-mediated inflammatory responses"],"prefix":"10.1093","volume":"215","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9908-2197","authenticated-orcid":false,"given":"Yoshikuni","family":"Goto","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences, Faculty of Pharmaceutical Sciences, Teikyo Heisei University , Nakano, Tokyo,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuko","family":"Ogawa","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Faculty of Pharmaceutical Sciences, Teikyo Heisei University , Nakano, Tokyo,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenji","family":"Ogawa","sequence":"additional","affiliation":[{"name":"Laboratory of Veterinary Epizootiology, Department of Veterinary Medicine, Nihon University , Fujisawa, Kanagawa,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1213-4439","authenticated-orcid":false,"given":"Atsushi","family":"Ohnishi","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Faculty of Pharmaceutical Sciences, Teikyo Heisei University , Nakano, Tokyo,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuma","family":"Aoki","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Faculty of Pharmaceutical Sciences, Teikyo Heisei University , Nakano, Tokyo,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1702-9278","authenticated-orcid":false,"given":"Takahiro J","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Laboratory of Animal Physiology, School of Agriculture, Meiji University , Kawasaki, Kanagawa,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masayuki","family":"Nakanishi","sequence":"additional","affiliation":[{"name":"Laboratory of Biochemistry, School of Pharmaceutical Sciences, Matsuyama University , Matsuyama, Ehime,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,7,16]]},"reference":[{"key":"2026090710451123400_vkag193-B1","first-page":"24","article-title":"Antibiotic activity of Bacillus polymyxa","volume":"54","author":"Benedict","year":"1947","journal-title":"J Bacteriol"},{"key":"2026090710451123400_vkag193-B2","first-page":"457","article-title":"A new antibiotic \u201ccolistin\u201d produced by spore-forming soil bacteria","volume":"3","author":"Koyama","year":"1950","journal-title":"J Antibiot (Tokyo)"},{"key":"2026090710451123400_vkag193-B3","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1146\/annurev.bi.46.070177.003451","article-title":"Polymyxin and related peptide antibiotics","volume":"46","author":"Storm","year":"1977","journal-title":"Annu Rev 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