{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T00:57:22Z","timestamp":1790902642673,"version":"4.1.0"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2012,12,20]],"date-time":"2012-12-20T00:00:00Z","timestamp":1355961600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"U.S. Food and Drug Administration, Center for Drug Evaluation and Research"},{"DOI":"10.13039\/100000002","name":"U.S. National Institutes of Health","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,12,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Interferon-alpha and interferon-lambda induce distinct functional responses in human hepatocytes, lymphocytes, and monocytes.<\/jats:p>\n               <jats:p>This study compared the ability of IFN-\u03b1 and IFN-\u03bb to induce signal transduction and gene expression in primary human hepatocytes, PBLs, and monocytes. IFN-\u03b1 drug products are widely used to treat chronic HCV infection; however, IFN-\u03b1 therapy often induces hematologic toxicities as a result of the broad expression of IFNARs on many cell types, including most leukocytes. rIFN-\u03bb1 is currently being tested as a potential alternative to IFN-\u03b1 for treating chronic HCV. Although IFN-\u03bb has been shown to be active on hepatoma cell lines, such as HepG2 and Huh-7, its ability to induce responses in primary human hepatocytes or leukocytes has not been examined. We found that IFN-\u03bb induces activation of Jak\/STAT signaling in mouse and human hepatocytes, and the ability of IFN-\u03bb to induce STAT activation correlates with induction of numerous ISGs. Although the magnitude of ISG expression induced by IFN-\u03bb in hepatocytes was generally lower than that induced by IFN-\u03b1, the repertoire of regulated genes was quite similar. Our findings demonstrate that although IFN-\u03b1 and IFN-\u03bb signal through distinct receptors, they induce expression of a common set of ISGs in hepatocytes. However, unlike IFN-\u03b1, IFN-\u03bb did not induce STAT activation or ISG expression by purified lymphocytes or monocytes. This important functional difference may provide a clinical advantage for IFN-\u03bb as a treatment for chronic HCV infection, as it is less likely to induce the leukopenias that are often associated with IFN-\u03b1 therapy.<\/jats:p>","DOI":"10.1189\/jlb.0812395","type":"journal-article","created":{"date-parts":[[2012,12,22]],"date-time":"2012-12-22T05:47:44Z","timestamp":1356155264000},"page":"377-385","source":"Crossref","is-referenced-by-count":96,"title":["Interferon-lambda (IFN-\u03bb) induces signal transduction and gene expression in human hepatocytes, but not in lymphocytes or monocytes"],"prefix":"10.1093","volume":"93","author":[{"given":"Harold","family":"Dickensheets","sequence":"first","affiliation":[{"name":"Division of Therapeutic Proteins, Center for Drug Evaluation and Research, U.S. Food and Drug Administration , Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faruk","family":"Sheikh","sequence":"additional","affiliation":[{"name":"Division of Therapeutic Proteins, Center for Drug Evaluation and Research, U.S. Food and Drug Administration , Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ogyi","family":"Park","sequence":"additional","affiliation":[{"name":"Laboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health , Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Gao","sequence":"additional","affiliation":[{"name":"Laboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health , Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raymond P","family":"Donnelly","sequence":"additional","affiliation":[{"name":"Division of Therapeutic Proteins, Center for Drug Evaluation and Research, U.S. Food and Drug Administration , Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2012,12,20]]},"reference":[{"key":"2023012312530634900_B1","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1038\/nrd2422","article-title":"Interferons at age 50: past, current and future impact on biomedicine","volume":"6","author":"Borden","year":"2007","journal-title":"Nat. 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