{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T14:40:02Z","timestamp":1790692802607,"version":"4.1.0"},"reference-count":57,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2021,6,8]],"date-time":"2021-06-08T00:00:00Z","timestamp":1623110400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010081","name":"Conseil R\u00e9gional de La R\u00e9union","doi-asserted-by":"publisher","award":["CPER-FEDER, VIROPAM Program"],"award-info":[{"award-number":["CPER-FEDER, VIROPAM Program"]}],"id":[{"id":"10.13039\/501100010081","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Alphaviruses are a group of arboviruses that generate chronic inflammatory rheumatisms in humans. Currently, no approved vaccines or antiviral therapies are available to prevent or treat alphavirus-induced diseases. The aim of this study was to evaluate the repositioning of the anti-cancer molecule irinotecan as a potential modulator of the antiviral and inflammatory responses of primary human synovial fibroblasts (HSF), the main stromal cells of the joint synovium. HSF were exposed to O\u2019nyong-nyong virus (ONNV) and polyinosinic-polycytidylic acid (PIC) to mimic, respectively, acute and chronic infectious settings. The cytokine IL-1\u03b2 was used as a major pro-inflammatory cytokine to stimulate HSF. Quantitative RT-PCR analysis revealed that irinotecan at 15 \u00b5M was able to amplify the antiviral response (i.e., interferon-stimulated gene expression) of HSF exposed to PIC and reduce the expression of pro-inflammatory genes (CXCL8, IL-6 and COX-2) upon IL-1\u03b2 treatment. These results were associated with the regulation of the expression of several genes, including those encoding for STAT1, STAT2, p53 and NF-\u03baB. Irinotecan did not modulate these responses in both untreated cells and cells stimulated with ONNV. This suggests that this drug could be therapeutically useful for the treatment of chronic and severe (rather than acute) arthritis due to viruses.<\/jats:p>","DOI":"10.3390\/cells10061431","type":"journal-article","created":{"date-parts":[[2021,6,8]],"date-time":"2021-06-08T12:08:55Z","timestamp":1623154135000},"page":"1431","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Irinotecan (CPT-11) Canonical Anti-Cancer Drug Can also Modulate Antiviral and Pro-Inflammatory Responses of Primary Human Synovial Fibroblasts"],"prefix":"10.3390","volume":"10","author":[{"given":"Anthony","family":"Dobi","sequence":"first","affiliation":[{"name":"Unit\u00e9 de Recherche en Pharmaco-Immunologie (UR-EPI), Universit\u00e9 et CHU de La R\u00e9union (Site F\u00e9lix Guyon), 97400 Saint-Denis, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Gasque","sequence":"additional","affiliation":[{"name":"Unit\u00e9 de Recherche en Pharmaco-Immunologie (UR-EPI), Universit\u00e9 et CHU de La R\u00e9union (Site F\u00e9lix Guyon), 97400 Saint-Denis, France"},{"name":"Laboratoire d\u2019Immunologie Clinique et Exp\u00e9rimentale de la Zone Oc\u00e9an Indien (LICE-OI), P\u00f4le de Biologie, CHU de La R\u00e9union (Site F\u00e9lix Guyon), 97400 Saint-Denis, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascale","family":"Guiraud","sequence":"additional","affiliation":[{"name":"Unit\u00e9 de Recherche en Pharmaco-Immunologie (UR-EPI), Universit\u00e9 et CHU de La R\u00e9union (Site F\u00e9lix Guyon), 97400 Saint-Denis, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9950-2542","authenticated-orcid":false,"given":"Jimmy","family":"Selambarom","sequence":"additional","affiliation":[{"name":"Unit\u00e9 de Recherche en Pharmaco-Immunologie (UR-EPI), Universit\u00e9 et CHU de La R\u00e9union (Site F\u00e9lix Guyon), 97400 Saint-Denis, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"129","DOI":"10.7861\/clinmedicine.16-2-129","article-title":"Viral arthritis","volume":"16","author":"Marks","year":"2016","journal-title":"Clin. 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