{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T02:11:52Z","timestamp":1792289512888,"version":"4.4.0"},"reference-count":34,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2017,3,2]],"date-time":"2017-03-02T00:00:00Z","timestamp":1488412800000},"content-version":"vor","delay-in-days":29,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Scand J Immunol"],"published-print":{"date-parts":[[2017,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>To date, selective blockade of Toll\u2010like receptor (<jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>) signalling has been developed as a new approach for treatment for many inflammatory diseases. As <jats:italic>\u03b2<\/jats:italic>\u2010D\u2010mannuronic acid (M2000) has been known as an anti\u2010inflammatory molecule in several experimental models, we investigated the antagonistic effects of M2000 on <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>2 and <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>4 downstream signalling transduction pathway in human embryonic kidney (<jats:styled-content style=\"fixed-case\">HEK<\/jats:styled-content>) 293 cell lines overexpressing <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>2\/<jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>14 and the <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>4\/<jats:styled-content style=\"fixed-case\">MD<\/jats:styled-content>2\/<jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>14 complex, respectively. M2000 effectively inhibited <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> expression of MyD88 and p65, major subunit of nuclear factor\u2010<jats:italic>\u03ba<\/jats:italic>B, in <jats:styled-content style=\"fixed-case\">HEK<\/jats:styled-content>293 cells stimulated by lipoteichoic acid (<jats:styled-content style=\"fixed-case\">LTA<\/jats:styled-content>, a <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>2 agonist) and lipopolysaccharide (<jats:styled-content style=\"fixed-case\">LPS<\/jats:styled-content>, a <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>4 agonist) with no evidence of cytotoxicity. In addition, M2000 also suppressed <jats:styled-content style=\"fixed-case\">LTA<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">LPS<\/jats:styled-content>\u2010induced production of <jats:styled-content style=\"fixed-case\">TNF<\/jats:styled-content>\u2010<jats:italic>\u03b1<\/jats:italic> and <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20106 inflammatory cytokines in these cells. Furthermore, the results revealed that M2000 had no significant effect on Tollip <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> expression as a negative regulator of <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content> signalling in aforesaid cells. Overall, these data point to M2000 inhibitory effect on Toll\u2010like receptor (<jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>) 2, 4 signalling in <jats:styled-content style=\"fixed-case\">HEK<\/jats:styled-content>293 cells. This information might provide new insights into the possible roles of this small drug in order to introduce it as a <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content> signalling pathway inhibitor. However, more studies are needed to confirm <jats:italic>\u03b2<\/jats:italic>\u2010D\u2010mannuronic acid antagonistic effects including the effects of M2000 on peritoneal isolated macrophages and also on blood cells in patients with inflammatory diseases such as ankylosing spondylitis.<\/jats:p>","DOI":"10.1111\/sji.12519","type":"journal-article","created":{"date-parts":[[2016,12,10]],"date-time":"2016-12-10T12:24:54Z","timestamp":1481372694000},"page":"122-129","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["M2000 (<i>\u03b2<\/i>\u2010D\u2010Mannuronic Acid) as a Novel Antagonist for Blocking the <scp>TLR<\/scp>2 and <scp>TLR<\/scp>4 Downstream Signalling Pathway"],"prefix":"10.1111","volume":"85","author":[{"given":"S.","family":"Aletaha","sequence":"first","affiliation":[{"name":"Department of Immunology School of Public Health Tehran University of Medical Sciences Tehran 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