L50
Patterns of Interferon Regulatory Factor 1 (IRF1) Expression By Respiratory Epithelial Cells Reveal Non-Redundancy of Type I Versus Type III Interferons
Sunday, March 6, 2016
South Exhibit Hall H (Convention Center)
Ronald L. Rabin, MD, Hilary Novatt, Terence C. Theisen, Lynnsey A. Renn
Rationale: Types I and III interferon (IFN) are co-expressed by respiratory epithelial cells (REC) in response to viral infection, and 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 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.

Methods: We treated BEAS-2B human REC with increasing doses of IFN-beta or IFN-lambda1 alone or together, and measured expression of TF-ISG and a set of “canonical” ISG by qRT-PCR and western blot.

Results: Alone, IFN-beta and IFN-lambda each induced expression of the canonical ISG and a subset of TF-ISG. By contrast, while IFN-beta alone induced IRF1 expression, it was poorly induced by IFN-lambda1 alone. Saturating doses of the two IFNs together did not enhance peak ISG transcript expression greater than either alone. Western blots revealed that while IFN-beta alone induced early and transient IRF1 expression, it was lower but sustained (through 24h) after IFN-lambda1 alone. In contrast to transcripts, saturating doses of the two IFNs together enhanced expression of IRF1 protein at 2h, 4h, and 24h greater than either of them alone.

Conclusions: In REC, IRF1 is expressed early and relatively selectively in response to IFN-beta alone, and protein expression was enhanced after treatment with both IFNs together. IRF1 may mediate non-redundant qualitative functional responses of REC to types I and III IFN.