{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T03:56:25Z","timestamp":1784865385118,"version":"3.55.0"},"reference-count":26,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2024,6,23]],"date-time":"2024-06-23T00:00:00Z","timestamp":1719100800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["22K07862"],"award-info":[{"award-number":["22K07862"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["FEBS Open Bio"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:p>Viral infections in tubular epithelial cells lead to the production of inflammatory cytokines by innate immunity, causing tubulointerstitial nephritis. TLR3 recognizes viral infections and acts via the activation of interferon (IFN)\/IFN\u2010stimulated genes (ISGs). This study investigates the role of ISG56, a representative ISG, in TLR3 signaling in cultured human renal proximal tubular epithelial cells (hRPTECs). To this end, hRPTECs were stimulated by a synthetic TLR3 ligand, polyinosinic\u2010polycytidylic acid (poly IC), recombinant human interferon\u2010\u03b2 [r(h)IFN\u2010\u03b2] or Japanese encephalitis virus (JEV) infection and assayed for inflammatory cytokine mRNA expression by RT\u2010qPCR, and protein expression via western blotting or ELISA. ISG56 was expressed by poly IC or r(h)IFN\u2010\u03b2 and IFN\u2010\u03b2 knockdown reduced poly IC\u2010induced expression of ISG56 and CXCL10. Moreover, ISG56 knockdown reduced poly IC\u2010 or r(h)IFN\u2010\u03b2\u2010induced expression of CXCL10 at the same time as increasing JEV growth and reducing CXCL10 expression induced by JEV infection. Overall, TLR3 signaling induced IFN\u2010\u03b2\u2010dependent expression of ISG56 and CXCL10. We show that ISG56 possibly plays a critical role in antiviral immunity of hRPTECs by positive regulation of IFN\u2010\u03b2\u2010mediated CXCL10 expression downstream of TLR3.<\/jats:p>","DOI":"10.1002\/2211-5463.13851","type":"journal-article","created":{"date-parts":[[2024,6,23]],"date-time":"2024-06-23T23:45:13Z","timestamp":1719186313000},"page":"1303-1319","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Interferon\u2010stimulated gene 56 positively regulates Toll\u2010like receptor 3\u2010mediated\n                    <scp>CXCL<\/scp>\n                    10 expression in human renal proximal tubular epithelial cells"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-7343-9121","authenticated-orcid":false,"given":"Mayuki","family":"Tachizaki","sequence":"first","affiliation":[{"name":"Department of Vascular and Inflammatory Medicine Hirosaki University Graduate School of 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