{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T09:49:09Z","timestamp":1792057749457,"version":"4.4.0"},"reference-count":55,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Hemin, an oxidized heme species released during erythrocyte breakdown, is detectable in gingival crevicular fluid during periodontal inflammation, but its effects on local immune signaling remain unclear. We investigated whether hemin modifies cytokine-induced interferon responses in HSC-2 oral squamous cell carcinoma cells and primary human gingival fibroblasts.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Cells were stimulated with interleukin-1\u03b2 and tumor necrosis factor-\u03b1, or with interferon-\u03b3, in the presence or absence of hemin. Transcriptomic changes were assessed by RNA sequencing and pathway analysis, and selected transcripts and proteins were validated by reverse-transcription quantitative PCR, enzyme-linked immunosorbent assay, immunoblotting, and immunofluorescence. Ligand\u2013kinase interactions were examined by molecular docking and molecular dynamics simulations, and recombinant Janus kinase 2 activity was measured in a cell-free assay.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Hemin preferentially suppressed an interferon-associated gene network, including CXCL10, CXCL11, MX1, OAS1, IFIT1, IFIT3, and ISG15, while nuclear factor \u03baB-associated responses were comparatively preserved. Hemin also reduced signal transducer and activator of transcription 1 Tyr701 phosphorylation and nuclear accumulation induced by either the cytokine combination or interferon-\u03b3. Computational analyses predicted stable hemin interactions within conserved ATP-binding pockets of Janus kinases, and the cell-free assay demonstrated inhibition of recombinant Janus kinase 2.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Together, these findings show that hemin attenuates interferon-associated transcription in periodontal cell models, consistent with inhibition of the Janus kinase 2\u2013signal transducer and activator of transcription 1 axis. This mechanism may enable blood-derived hemin to modify local mucosal immune signaling, although its relevance to periodontal tissues and antiviral defense requires confirmation in organotypic, infection, and in vivo models.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1958476","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T06:04:54Z","timestamp":1790748294000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Hemin suppresses interferon responses in periodontal cell models through JAK2\u2013STAT1 inhibition"],"prefix":"10.3389","volume":"17","author":[{"given":"Xiaoyu","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Oral Biology, Medical University of Vienna","place":["Vienna, Austria"]},{"name":"Department of Prosthodontics, The Affiliated Stomatological Hospital of Southwest Medical University","place":["Luzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reinhard","family":"Gruber","sequence":"additional","affiliation":[{"name":"Department of Oral Biology, Medical University of Vienna","place":["Vienna, Austria"]},{"name":"Department of Periodontology, School of Dental Medicine, University of Bern","place":["Bern, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Layla","family":"Panahipour","sequence":"additional","affiliation":[{"name":"Department of Oral Biology, Medical University of Vienna","place":["Vienna, Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"17038","DOI":"10.1038\/nrdp.2017.38","article-title":"Periodontal diseases","volume":"3","author":"Kinane","year":"2017","journal-title":"Nat Rev Dis Primers"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1111\/jcpe.12945","article-title":"Staging and grading of periodontitis: Framework and proposal of a new classification and case definition","volume":"45","author":"Tonetti","year":"2018","journal-title":"J Clin Periodontology"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1111\/jre.13337","article-title":"Burden of severe periodontitis and edentulism in 2021, with projections up to 2050: The global burden of disease 2021 study","volume":"59","author":"Nascimento","year":"2024","journal-title":"J Periodontal Res"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0757.1996.tb00080.x","article-title":"Monitoring disease during supportive periodontal treatment by bleeding on probing","volume":"12","author":"Lang","year":"1996","journal-title":"Periodontol 2000"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-051x.1994.tb00737.x","article-title":"Bleeding on probing. 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