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TAK-242, a TLR4 blocker, has been found to have a significant impact on the gene expression profile of pro-inflammatory cytokines such as IL1-\u03b2, IL-6, TNF-\u03b1, and TLR4, as well as the phosphorylation of Ik\u03b2\u03b1, a regulator of the NF-\u03baB signaling pathway, in OA-FLSs. This study aims to investigate this effect because TLR4 plays a crucial role in inflammatory responses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>\n                      Ten OA patients\u2019 synovial tissues were acquired, and isolated FLSs were cultured in DMEM in order to assess the effectiveness of TAK-242. The treated FLSs with TAK-242 and Lipopolysaccharides (LPS) were analyzed for the mRNA expression level of\n                      <jats:italic>IL1-\u03b2, IL-6, TNF-\u03b1<\/jats:italic>\n                      , and\n                      <jats:italic>TLR4<\/jats:italic>\n                      levels by Real-Time PCR. Besides, we used western blot to assess the protein levels of Ik\u03b2\u03b1 and pIk\u03b2\u03b1.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The results represented that TAK-242 effectively suppressed the gene expression of inflammatory cytokines\n                      <jats:italic>IL1-\u03b2<\/jats:italic>\n                      ,\n                      <jats:italic>IL-6<\/jats:italic>\n                      ,\n                      <jats:italic>TNF-\u03b1<\/jats:italic>\n                      , and\n                      <jats:italic>TLR4<\/jats:italic>\n                      which were overexpressed upon LPS treatment. Additionally, TAK-242 inhibited the phosphorylation of Ik\u03b2\u03b1 which was increased by LPS treatment.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>According to our results, TAK-242 shows promising inhibitory effects on TLR4-mediated inflammatory responses in OA-FLSs by targeting the NF-\u03baB pathway. TLR4 inhibitors, such as TAK-242, may be useful therapeutic agents to reduce inflammation and its associated complications in OA patients, since traditional and biological treatments may not be adequate for all of them.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s42358-024-00385-9","type":"journal-article","created":{"date-parts":[[2024,6,7]],"date-time":"2024-06-07T05:01:54Z","timestamp":1717736514000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["TAK-242 (Resatorvid) inhibits proinflammatory cytokine production through the inhibition of NF-\u03baB signaling pathway in fibroblast-like synoviocytes in osteoarthritis patients"],"prefix":"10.1186","volume":"64","author":[{"given":"Mohammadreza","family":"Khomeijani-Farahani","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jafar","family":"karami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elham","family":"Farhadi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samaneh","family":"Soltani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali-Akbar","family":"Delbandi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehdi","family":"Shekarabi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad Naghi","family":"Tahmasebi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arash Sharafat","family":"Vaziri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmadreza","family":"Jamshidi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8164-8831","authenticated-orcid":false,"given":"Mahdi","family":"Mahmoudi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masoomeh","family":"Akhlaghi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,6,7]]},"reference":[{"issue":"1","key":"385_CR1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.rdc.2012.10.004","volume":"39","author":"T Neogi","year":"2013","unstructured":"Neogi T, Zhang Y. 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