Investigation of inflammasome components during cell migration process in autoinflammatory diseases

Akbaba, T.H., Investigation of Inflammasome Components During Cell Migration Process in Autoinflammatory Diseases. Hacettepe University, Institute of Health Sciences, M.Sc. Thesis in Medical Biology, Ankara, 2019. Autoinflammatory diseases, periodic fever syndromes, are a group of diseases that develop recurrent inflammatory response in the absence of infection. Familial Mediterranean fever, which is the most common disease among autoinflammatory diseases, is caused by mutant pyrin production due to mutations in MEFV gene. Pyrin protein is thought to be involved in inflammatory pathways by means of protein-protein interactions. There are studies supporting the role of pyrin as a proinflammatory regulator in the literature and involved in pathways associated with cell migration. Within the scope of the thesis; pyrin inflammasome was examined in mononuclear cells isolated from the blood samples of 11 FMF patients, other autoinflammatory diseases; 2 HIDS patients, 1 CAPS patient and 7 healthy individuals in the process of inflammatory cell migration. Lipopolysaccharide was used to induce the activation of inflammasome in the cells, while arachidonic acid was used for the inhibition of inflammasome. As a result of the experiments, it was found that the inhibition of inflammation compared to the controls was less in the cells of FMF patients under the same application conditions. Following inflammasome activation and inhibition, filter experiments were performed and fetal bovine serum was used to induce inflammatory cell migration. When the inflammasome was suppressed, a statistically significant increase was found in both inflammasome activation and the ratio of cell migration of the mononuclear cells of the FMF patients compared to other autoinflammatory disease patients and control indivuals' mononuclear cells (p<0.0156 and p<0,0286). These findings support the idea of increased cell migration ratio in patients with FMF due to the more active pyrin inflammasome. This thesis has made significant contributions to illuminate the role of pyrin protein in inflammatory cell migration through the structure of inflammasome. Keywords: Autoinflammatory diseases, FMF, pyrin inflammasome, cell migration. This thesis was supported by Hacettepe University Scientific Research Coordination Unit (Project Number: TYL-2018-17354)