{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T12:21:46Z","timestamp":1787746906145,"version":"build-2784847793"},"reference-count":57,"publisher":"SAGE Publications","issue":"17-18","license":[{"start":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T00:00:00Z","timestamp":1780531200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"T\u00fcrkiye Bilimsel ve Teknolojik Ara\u015ft?rma Kurumu","award":["113S375"],"award-info":[{"award-number":["113S375"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Human Gene Therapy"],"published-print":{"date-parts":[[2026,9,1]]},"abstract":"<jats:p>\n                    Rheumatoid arthritis is a chronic autoimmune disease characterized by persistent synovial inflammation and progressive joint destruction. Although biological disease-modifying anti-rheumatic drugs (DMARDs) have transformed treatment, their systemic immunosuppression, high cost, and incomplete efficacy in certain joints remain significant challenges. To address these limitations, we developed a localized gene therapy using the human indoleamine 2,3-dioxygenase (\n                    <jats:italic toggle=\"yes\">hIDO<\/jats:italic>\n                    ) gene driven by the E-selectin (ELAM-1) promoter, which is responsive to inflammatory cytokines. We assessed ELAM-1 promoter responsiveness to interleukin-1\u03b2 (IL-1\u03b2) stimulation\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    mainly using the HeLa cell line, measuring\n                    <jats:italic toggle=\"yes\">hIDO<\/jats:italic>\n                    expression and enzymatic activity by enzyme-linked immunosorbent assay, quantitative reverse transcription-polymerase chain reaction (qRT-PCR), Western blotting and kynurenine assays.\n                    <jats:italic toggle=\"yes\">In vivo<\/jats:italic>\n                    , we established a robust collagen-induced arthritis (CIA) model in BALB\/c mice, which are normally resistant to CIA, and delivered pELAM-1pro\/hIDO plasmids intra-articularly via liposomes. Therapeutic efficacy was evaluated by clinical scoring, ankle circumference, histopathology, immunohistochemical quantification of synovial CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells and CD68\n                    <jats:sup>+<\/jats:sup>\n                    macrophages, and endpoint immunohistochemical assessment of IDO expression.\n                    <jats:italic toggle=\"yes\">In vitro<\/jats:italic>\n                    , the ELAM-1 promoter allowed rapid, high-level expression of hIDO within 2 h of IL-1\u03b2 stimulation, without IDO-induced suppression of the promoter.\n                    <jats:italic toggle=\"yes\">In vivo<\/jats:italic>\n                    , pELAM-1pro\/hIDO treatment significantly reduced ankle swelling and clinical arthritis scores more rapidly than constitutive CMV-driven hIDO, achieving marked histological improvement on day 7. The treated joints exhibited substantial reductions in pathogenic CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells and CD68\n                    <jats:sup>+<\/jats:sup>\n                    macrophages, consistent with the IDO immunoregulatory mechanism. This study supports the feasibility of a localized gene therapy approach using an inflammation-responsive promoter and suggests localized immunomodulation at disease sites in a manner consistent with inflammation-associated promoter activity.\n                  <\/jats:p>","DOI":"10.1177\/10430342261452520","type":"journal-article","created":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T07:10:36Z","timestamp":1780557036000},"page":"833-848","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Inflammation-Inducible Expression of Human Indoleamine 2,3-Dioxygenase Driven by the E-Selectin Promoter Ameliorates Collagen-Induced Arthritis"],"prefix":"10.1177","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5301-6626","authenticated-orcid":false,"given":"Mehmet","family":"Kara\u00e7ay","sequence":"first","affiliation":[{"name":"Department of Medicine-Immunology, Institute of Health Sciences, Bursa Uludag University, Bursa, T\u00fcrkiye"},{"name":"Division of Medical Genetics, Department of Internal Medicine, Faculty of Medicine, Van Yuzuncu Yil University, Van, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u0130zel","family":"Y\u0131lmaz","sequence":"additional","affiliation":[{"name":"Department of Medicine-Immunology, Institute of Health Sciences, Bursa Uludag University, Bursa, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ay\u015fe \u00d6zden","family":"Barazi Soyda\u015f","sequence":"additional","affiliation":[{"name":"Department of Immunology, Graduate School of Health Sciences, Gazi University, Ankara, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00f6k\u00e7en","family":"G\u00fcven\u00e7-Bayram","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Veterinary Medicine, Dokuz Eylul University, Izmir, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Figen","family":"Ersoy","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genetics, Bursa Uludag University, Bursa, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cansel G\u00fczin","family":"\u00d6zg\u00fcden Akko\u00e7","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Faculty of Veterinary Medicine, Bursa Uludag University, Bursa, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arzu","family":"Y\u0131lmaztepe Oral","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Faculty of Medicine, Bursa Uludag University, Bursa, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmet","family":"Akko\u00e7","sequence":"additional","affiliation":[{"name":"Department of Pathology, Faculty of Veterinary Medicine, Bursa Uludag 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