IFNα enhances the production of IL-6 by human neutrophils activated via TLR8
| Autor: | Francisco Bianchetto-Aguilera, Federica Calzetti, Fabio Arruda-Silva, Giulia Finotti, Maili Zimmermann, Marco A. Cassatella, Nicola Tamassia, Patrizia Scapini, Claudio Lunardi |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Adult Cell Survival Neutrophils medicine.medical_treatment SLE IFNalpha Article 03 medical and health sciences Young Adult 0302 clinical medicine medicine Humans Lupus Erythematosus Systemic Interleukin 6 Receptor Autocrine signalling Promoter Regions Genetic TLR8 Aged IL-6 Multidisciplinary Innate immune system biology business.industry Interleukin-6 Tumor Necrosis Factor-alpha CCAAT-Enhancer-Binding Protein-beta Gene Expression Profiling neutrophils Imidazoles Interferon-alpha TLR7 Middle Aged 030104 developmental biology Cytokine Gene Expression Regulation Toll-Like Receptor 7 Genetic Loci Toll-Like Receptor 8 Immunology biology.protein Tumor necrosis factor alpha Female business 030215 immunology Protein Binding |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/srep19674 |
| Popis: | Recently, we reported that human neutrophils produce biologically active amounts of IL-6 when incubated with agonists activating TLR8, a receptor recognizing viral single strand RNA. In this study, we demonstrate that IFNα, a cytokine that modulates the early innate immune responses toward viral and bacterial infections, potently enhances the production of IL-6 in neutrophils stimulated with R848, a TLR8 agonist. We also show that such an effect is not caused by an IFNα-dependent induction of TLR7 and its consequent co-activation with TLR8 in response to R848, but, rather, it is substantially mediated by an increased production and release of endogenous TNFα. The latter cytokine, in an autocrine manner, leads to an augmented synthesis of the IkBζ co-activator and an enhanced recruitment of the C/EBPβ transcription factor to the IL-6 promoter. Moreover, we show that neutrophils from SLE patients with active disease state, hence displaying an IFN-induced gene expression signature, produce increased amounts of both IL-6 and TNFα in response to R848 as compared to healthy donors. Altogether, data uncover novel effects that type I IFN exerts in TLR8-activated neutrophils, which therefore enlarge our knowledge on the various biological actions which type I IFN orchestrates during infectious and autoimmune diseases. |
| Databáze: | OpenAIRE |
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