Screening of natural compounds affecting type I Interferon signalling

BOLLATI FOGOLÍN M. R.; OGGERO EBERHARDT, M.; MIRAZO, S.; FRANK, R.; KRATJE, R. B.; MÜLLER, W.

Dresden. Alemania

Congreso; 20th Meeting of the European Society for Animal Cell Technology (ESACT); 2007

European Society for Animal Cell Technology

Interferons (IFNs) are a family of cytokine mediators involved in the cellular immune response, i.e. against viral infections or amplifying antigen presentation to specific T cells. Recombinant human IFN-alpha±2a and IFN-alpha±2b are used for the treatment of chronic hepatitis B and C, follicular non-Hodking´s lymphoma, genital warts, hairy cell leukemia, amongst others, while recombinant forms of IFN-beta1a and IFN-beta1b are only certified for the treatment of multiple sclerosis. Recently, we have reported the generation of a novel cell-based assay to quantify murine IFNs (mIFN). The assay consists of a murine type I IFN induction phase, which drives the expression of Cre recombinase from the Mx/RAGE cell line. Cre-recombinase mediated deletion of loxP flanked resistance cassette leads to EGFP expression. The read-out of the system consists of the detection of EGFP positive cells by fluorescence activated cell sorting (FACS) or fluorescence microscopy. One of the advantages of this method is that allows the design of robust high through put screening assays. Taking these together, in the present work, we aim to select natural compounds able to induce or interfere with murine type I IFN signaling. Screening of a library composed of 115 natural compounds from the myxococcal metabolite collection of the HZI yielded twelve compounds showing a synergistic effect with more than 3-fold increase on the mIFN activity. Characterization of the immunomodulatory, antiviral, virucide and antiproliferative effect of these hits has been undertaken in order to assess their potential application for the treatment of IFN-related disease.