Abstract
Abstract Types I and III interferon (IFN) are co-expressed by respiratory epithelial cells (REC) in response to viral infection. In turn, these IFN stimulate neighboring REC to express a set of interferon-stimulated genes (ISG) through shared signaling pathways. Whether types I and III IFN have non-redundant functions in anti-viral defense of respiratory infections is unknown. Because transcription factors dictate cellular phenotype and function, we hypothesized that ISG that are transcription factors (TF-ISG) mediate non-redundant functions of types I or III IFN. We treated BEAS-2B human REC with increasing doses of IFN-β or IFN-λ1 alone or together, and measured expression of TF-ISG and a set of canonical ISG by qRT-PCR and Western blot. Alone, IFN-β and IFN-λ1 each induced expression of canonical ISG and a subset of TF-ISG. Expression of several ISG differed in response to type I versus type III IFN, either in peak levels or kinetic patterns, or both. Uniquely, IRF1 is induced early in response to IFN-β alone, but is poorly expressed in response to IFN-λ1. Western blots also revealed that while IFN-β alone induced early and transient IRF1 expression, it was lower but sustained (through 24h) after IFN-λ1 alone. In contrast to transcript expression, the two IFN together enhanced expression of IRF1 protein greater than either alone, and IRF1 expression was sustained through 24h. The distinct selective and rapid expression of IRF1 transcript and protein in response to IFN-β suggests that this TF-ISG mediates non-redundant qualitative functional responses of REC to types I and III IFN.
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