RESUMO
Type I and type III interferons (IFNs) are induced by viral infection. It was concluded that these IFN species are identical in regulation and biological functions. However, these two systems differ in the tissue expression of their receptors and their transcriptional regulation is fundamentally different as well as cellular signaling pathways that drive expression of each IFN. Here, we have investigated the transcriptional profile of endogenous IFNs after stimulation of cells with exogenous IFNs and subsequent infection of A549 cells with A/chicken/Germany/27 [H7N7] influenza virus. Both type I and type III IFNs exhibit high degree of the cross-induction. Our results show that type III IFNs (IFN-λ1, IFN-λ2 and IFN-λ3) are better inducers of CXCL10 than type I IFNs. The IFN-ß1a and IFN-λ2 were the most potent IFNs and they highly increased the level of IFN-α, IFN-ß, IFN-λ, and CXCL10 mRNAs. Since type I IFNs up regulated expression of retinoic acid-inducible gene 1 (RIG-1) mRNA, type III IFNs-λ down regulated expression of RIG-1 mRNA in influenza infected cells. IFN-α and IFN-ω induced similar amount of IFN-α, IFN-ß and IFN-λ mRNA but differ in induction of CXCL10 and RIG-1 mRNA.
Assuntos
Quimiocina CXCL10/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Interferons/farmacologia , Receptores do Ácido Retinoico/metabolismo , Transcrição Gênica , Transcriptoma , Adenocarcinoma , Linhagem Celular Tumoral , Quimiocina CXCL10/genética , Regulação da Expressão Gênica/imunologia , Humanos , Interferons/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores do Ácido Retinoico/genéticaRESUMO
The interferon system represents one of the components of the first line defence against influenza virus infection. Interferon omega (IFN-ω) is antigenetically different from IFN-α and IFN-ß and can affect patients who are resistant to these IFNs. To improve the biological characterization of IFN-ω, we compared its activity with those of type I and type III IFNs in induced A549 cells. The antiviral effect on IFN-stimulated A549 cells was most apparent after infection with avian influenza virus. IFN-ω had statistically significant antiviral activity although less than IFN-ß1a, IFN-λ1, or IFN-λ2. On the other hand, IFN-ω appeared more efficient than IFN-α2. Our results also indicate that IFN-λs were more suitable against human highly pathogenic virus. In this case, IFN-λ1 and IFN-λ2 were more potent than type I IFNs.
