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The metabolic role of pulmonary arterial fibroblasts in the activation of immune system during development of pulmonary arterial hypertension
Křivonosková, Monika ; Plecitá, Lydie (advisor) ; Zadražil, Zdeněk (referee)
The development of inflammation in the small distal pulmonary vessels plays an important role in the development of pulmonary arterial hypertension (PAH). One of the cell types found in the pulmonary vessels are fibroblasts, which, according to the "outside-in" theory, may be the first to respond to stimuli in the vessel, modulating remodeling of the pulmonary vessels toward the inner layers of the vessel and attracting other immune cells to the site. In addition to inflammation, the so- called Warburg effect also occurs in vessels affected by PAH, in which metabolism shifts toward glycolysis and lactate production. Among other changes, a pro-oxidative state is induced within the cell by mitochondrial metabolism and NADPH oxidase, leading to an imbalance in reactive oxygen species production. We therefore wanted to test whether calf lung fibroblasts with hypoxia-induced PAH have an active inflammasome, with which they would produce mature interleukin 1β (IL-1β) and to clarify the effect of a pro-oxidant environment on this expression. In our in vitro model we have confirmed IL-1β mRNA expression, but we were unable to detect its expression at the protein level. This was consistent with the inability to detect inflammasome activity. We believe that the inability to detect the protein form of IL-1β...
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The influence of inflammatory cytokines on depressive disorders
Svobodová, Eva ; Bendová, Zdeňka (advisor) ; Krulová, Magdaléna (referee)
1 Abstract Depressive disorders are one of the three most frequent diseases causing disability of everyday life of humans. Its occurrence in the population is rapidly increasing. Etiology of depression is unclear, and the treatment usually only ameliorates its symptoms. In patients, there were identified signs not only of chronic stress, which has been associated with depression for quite a long time, but also signs of chronic inflammation in the body. This has led to focusing on proinflammatory cytokines and their connection to chronic stress and depressive symptomatology. We are also interested in the causal link between pro-inflammatory markers and stress that has not yet been unequivocally clarified. The aim of this study is to combine the knowledge about the influence of chronic stress on the development of depressive disorder gained from animal and human models. Additionally, to combine the knowledge of the effect of specific proinflammatory cytokines on the development of the depressive disorder and the change in brain structures morphology which may underlie the symptoms of this disease.
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