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Regulation of STING function during murine polyomavirus infection
Šnejdarová, Aneta ; Horníková, Lenka (advisor) ; Pimková Polidarová, Markéta (referee)
Stimulator of Interferon Genes (STING) is the adapter protein of an innate immunity signalling pathway, involved in detection of double-stranded DNA (dsDNA) in the cell cytoplasm, which leads to the expression of pro-inflammatory genes, including the production of type I interferon. Eventhough during the infection with a dsDNA virus, murine polyomavirus (MPyV), the STING protein is activated, the resulting interferon production is moderate. Therefore, it can be assumed that the function of the STING protein is regulated in MPyV-infected cells. The aim of this thesis was to investigate three mechanisms by which the regulation can occur, namely through protein interaction partners, post- translational modifications, or changes in the subcellular localization of the STING protein. A cell-line of mouse fibroblasts stably expressing the STING protein fused with the HA-tag was established to facilitate the research. Furthermore, two plasmids were prepared, that encode the STING protein fused with the green fluorescent protein, facilitating the monitoring of the localization of the protein in the cell, or with a composite tag containing an in vivo biotinylated BioEaseTM -tag enabling effective isolation of the STING protein. The results of colocalization observations and coimmunoprecipitation suggest that...
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Immunosuppression in active multiple sclerosis: combination treatment with interferon beta and azathioprine and fingolimod monotherapy
Tichá, Veronika ; Kubala Havrdová, Eva (advisor) ; Vymazal, Josef (referee) ; Laczó, Jan (referee)
Introduction: Addition of a second drug used to be a strategy to achieve clinical stabilization of multiple sclerosis in many patients with on-going activity despite monotherapy. Modern immunosuppressive drugs used in monotherapy exert more specific mode of action. Methods: This retrospective observational study evaluated 5-year data from 85 patients with active multiple sclerosis despite monotherapy with either interferon beta or azathioprine, who received add-on azathioprine or interferon beta, respectively. In a subgroup of 23 patients 10- year data were analysed. In a second part of the study, a group of 126 patients switched either from interferon beta or glatiramer acetate to fingolimod was followed-up for one after the change of their treatment and a in a subgroup of 53 patients the 2-year data were assessed. Clinical (relapse frequency, disability) parameters were compared preceding and following the addition of second drug or the switch of treatment. Laboratory results and potential serious adverse events were evaluated in a group of patients with combination therapy. Results: The add-on treatment triggered a drop in annualised relapse rate by approximately 1.5 points sustained over 5 and 10 years. No effect on disability was observed. Simultaneously, white blood cell and lymphocyte counts...
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