Interferon-lambda (IFN-?) induces signal transduction and gene expression in human hepatocytes, but not in lymphocytes or monocytes.

ABSTRACT: This study compared the ability of IFN-? and IFN-? to induce signal transduction and gene expression in primary human hepatocytes, PBLs, and monocytes. IFN-? drug products are widely used to treat chronic HCV infection; however, IFN-? therapy often induces hematologic toxicities as a result of the broad expression of IFNARs on many cell types, including most leukocytes. rIFN-?1 is currently being tested as a potential alternative to IFN-? for treating chronic HCV. Although IFN-? 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-? induces activation of Jak/STAT signaling in mouse and human hepatocytes, and the ability of IFN-? to induce STAT activation correlates with induction of numerous ISGs. Although the magnitude of ISG expression induced by IFN-? in hepatocytes was generally lower than that induced by IFN-?, the repertoire of regulated genes was quite similar. Our findings demonstrate that although IFN-? and IFN-? signal through distinct receptors, they induce expression of a common set of ISGs in hepatocytes. However, unlike IFN-?, IFN-? did not induce STAT activation or ISG expression by purified lymphocytes or monocytes. This important functional difference may provide a clinical advantage for IFN-? as a treatment for chronic HCV infection, as it is less likely to induce the leukopenias that are often associated with IFN-? therapy.

SUBMITTER: Dickensheets H 

PROVIDER: S-EPMC3579021 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature