{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,8]],"date-time":"2025-11-08T17:47:18Z","timestamp":1762624038134,"version":"3.37.3"},"reference-count":54,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2018,6,14]],"date-time":"2018-06-14T00:00:00Z","timestamp":1528934400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100002462","name":"Chungnam National University","doi-asserted-by":"publisher","award":["2017\u20101919\u201001"],"award-info":[{"award-number":["2017\u20101919\u201001"]}],"id":[{"id":"10.13039\/501100002462","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2016\u20102288\u201002"],"award-info":[{"award-number":["2016\u20102288\u201002"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int Forum Allergy Rhinol"],"published-print":{"date-parts":[[2018,9]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Nasal polyposis is characterized by persistent inflammation and remodeling in sinonasal mucosa. Toll\u2010like receptor 9 (TLR9) is a DNA receptor of the innate immune system that plays a pivotal role in fibrosis and inflammatory responses. The aim of this study is to explore the expression, activity, and potential pathogenic role of TLR9 signaling in tissue remodeling in nasal polyp\u2013derived fibroblasts (NPDFs).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Fibrotic and inflammatory responses elicited by type A CpG oligonucleotides were examined in the NPDFs by a combination of real\u2010time quantitative polymerase chain reaction, Western blot analysis, enzyme\u2010linked immunosorbent assay, and immunofluorescence staining. For these experiments, the NPDFs were stimulated with different TLR9 agonists (CpG A and B) and blocked with inhibitors (MyD88 inhibitor and chloroquine).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>TLR9 expression was significantly higher in nasal polyposis (NP) tissues compared to control or chronic rhinosinusitis (CRS) mucosa. In the NPDFs, TLR9 showed intracellular localization and expression of TLR9 was increased after treatment with CpG A. CpG A increased production of \u03b1\u2010smooth muscle actin (\u03b1\u2010SMA), fibronectin, and matrix metalloproteinases (MMPs) (MMP1, MMP2, and MMP9) in the NPDFs, while MyD88 inhibitor and chloroquine, which are known to block the TLR9 signaling pathway, inhibited their production. CpG A also produced type I interferons (IFN\u2010\u03b1 and IFN\u2010\u03b2), which were inhibited by MyD88 inhibitor.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our data indicates that CpG A\u2013induced fibroblast activation and cytokine production were mediated via TLR9 stimulation in NPDFs. Disrupting this process with an inhibitor targeting TLR9 or its downstream signaling pathways could represent a novel approach to CRS with NP (CRSwNP) therapy.<\/jats:p><\/jats:sec>","DOI":"10.1002\/alr.22155","type":"journal-article","created":{"date-parts":[[2018,6,14]],"date-time":"2018-06-14T11:36:41Z","timestamp":1528976201000},"page":"1001-1012","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Role of Toll\u2010like receptor 9 signaling on activation of nasal polyp\u2013derived fibroblasts and its association with nasal polypogenesis"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5163-536X","authenticated-orcid":false,"given":"Soo Kyoung","family":"Park","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology\u2013Head and Neck Surgery Research Institute for Medical Science, Chungnam National University School of Medicine  Daejeon 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