{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T10:06:58Z","timestamp":1790330818324,"version":"4.1.0"},"reference-count":76,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Applied Toxicology"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Hexabromocyclododecane (HBCD), a brominated flame retardant, has raised increasing health concerns due to its bioaccumulation in human tissues and its ability to induce proinflammatory cytokines. Interleukin\u20101\u03b2 (IL\u20101\u03b2), interleukin\u20106 (IL\u20106), and tumor necrosis factor\u2010\u03b1 (TNF\u2010\u03b1) are major mediators of inflammation, and their chronic elevation contributes to autoimmune disorders, cardiovascular disease, and cancer. Previous studies have implicated mitogen\u2010activated protein kinases (MAPKs) as mediators of HBCD\u2010induced IL\u20101\u03b2 and IL\u20106 production. Because MAPKs act downstream of Toll\u2010like receptors (TLRs)\u2014key inflammatory response regulators, identifying whether TLRs contribute to HBCD\u2010driven inflammation is essential. This study examined the roles of TLR1\/2, TLR2, TLR3, TLR4, and TLR8 in HBCD\u2010induced IL\u20101\u03b2, IL\u20106, and TNF\u2010\u03b1 production in peripheral blood mononuclear cells (PBMCs). PBMCs were pretreated with selective inhibitors targeting TLR1\/2 (CUCPT 22), TLR2 (C29), TLR3 (CUCPT 4a), TLR4 (TAK\u2010242), TLR8 (CUCPT 9a), and MyD88 (TJ\u2010M2010\u20105), followed by exposure to HBCD (1\u20135\u2009\u03bcM). The results indicated that inhibition of TLR4 significantly reduced HBCD\u2010induced production of all three cytokines, demonstrating its central roles in this response. Blocking TLR8 significantly reduced HBCD\u2010induced IL\u20101\u03b2 production. In contrast, inhibition of TLR1\/2, TLR2, or TLR3 produced no consistent effects on HBCD\u2010induced cytokine production. Inhibition of the TLR\u2010associated adaptor protein MyD88 significantly attenuated HBCD\u2010induced IL\u20101\u03b2 and IL\u20106 production, whereas TNF\u2010\u03b1 production was not consistently affected. These results further elucidate the mechanism by which HBCD leads to elevation of pro\u2010inflammatory cytokine production by human immune cells.<\/jats:p>","DOI":"10.1002\/jat.70415","type":"journal-article","created":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T23:15:48Z","timestamp":1787786148000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Toll\u2010Like Receptors in the Mechanism of Hexabromocyclododecane\u2010Induced Production of Pro\u2010Inflammatory Cytokines"],"prefix":"10.1002","author":[{"given":"Wenjun","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Biology Tennessee State University  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-1062-6968","authenticated-orcid":false,"given":"Aleshia","family":"Seaton\u2010Terry","sequence":"additional","affiliation":[{"name":"Department of Biology Tennessee State University  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Townsend","sequence":"additional","affiliation":[{"name":"Department of Biology Tennessee State University  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zinia","family":"Hunter","sequence":"additional","affiliation":[{"name":"Department of Biology Tennessee State University  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2541-1987","authenticated-orcid":false,"given":"April","family":"Falconer\u2010Turner","sequence":"additional","affiliation":[{"name":"Department of Biology Tennessee State University  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Syeda Raika","family":"Shahid","sequence":"additional","affiliation":[{"name":"Department of Chemistry Tennessee State University  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1511-9181","authenticated-orcid":false,"given":"Margaret","family":"Whalen","sequence":"additional","affiliation":[{"name":"Department of Chemistry Tennessee State University  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,26]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1021\/es702378t"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19082244"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actatropica.2020.105458"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/90609"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tox.2022.153177"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells10061374"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.3109\/1547691X.2015.1111960"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1021\/es970009"},{"key":"e_1_2_9_10_1","unstructured":"Arnot J. 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