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The effect of stress on regulation and regeneration of glucocorticoids in animal models differing in response of hypothalamo-pituitary-adrenal axis
Vodička, Martin ; Pácha, Jiří (advisor) ; Svoboda, Jan (referee) ; Bendová, Zdeňka (referee)
Stress reaction is usually activated by the brain, when homeostasis is or perceived to be threatened. The stress signals are transmitted from the brain by two main branches; the sympathoadrenomedullary and the hypothalamo-pituitary-adrenal (HPA) axes and employ neural, humoral and immune pathways to cope with the stressor. Because of its potency, the stress reaction has to be precisely regulated. The HPA axis is regulated by feedback loops where its end product, corticosterone in laboratory rat and mouse, inhibits its activity. The effect of corticosterone does not depend only on the concentration of corticosterone but also on local metabolism of glucocorticoids via oxo-reduction catalyzed by the enzyme 11β -hydroxysteroid dehydrogenase 1 (encoded by the Hsd11b1 gene), which intracellularly regenerates active corticosterone from inactive 11-dehydrocorticosterone, or by extra-adrenal de novo steroidogenesis of glucocorticoids. We focused on analysis of stress response in experimental animals differing in HPA axis responsivity (Fischer 344 rats (F344) vs. Lewis rats (LEW) and germ-free (GF) vs. specific pathogen free mice (SPF)) with special emphasis on regulation of stress response, glucocorticoid regeneration and influence of gut microbiota. We found that stress modulated local regeneration of...
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The Mechanism of Pathogenesis of Experimental Autoimmune Uveitis and Possilbilities of Their Regulation
Klímová, Aneta ; Heissigerová, Jarmila (advisor) ; Pitrová, Šárka (referee) ; Holáň, Vladimír (referee)
Introduction:Uveitis in an ocular inflammation affecting mostly people of working age. Uveitis is responsible for severe visual impairment despite of expanding new therapeutics. The animal models of uveitis were established, because the wide clinical variability of uveitis limits the studies in human medicine. The goal our project was to establish a reproducible model of experimental autoimmune uveitis in Czech Republic, and further on this model to observe the frequency of CD3+ and F4/80+ cells in retina, to assess the influence of microbial environment on intensity of intraocular inflammation and to test the therapeutical possibilities. Material and methods: The C57BL/6J mice were immunized by retinal antigen (IRBP 1-20, interphotoreceptor retinoid binding protein), enhanced by complete Freund's adjuvant and pertussis toxin and mild posterior autoimmune uveitis was induced. The mice were bred in conventional and germ-free (gnotobiotic) conditions. The uveitis intensity was evaluated in vivo biomicroscopically and post mortem histologically on hematoxylin eosin stained sections according to the standard protocol. The histological eye specimen were analyzed also by imunohistochemisty and by flow cytometry. Each experiment was performed for 35 days. The conventional mice with uveitis were treated...
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Impact of Probiotic Bacteria on Allergic Sensitization in Type I Allergy Model
Schwarzer, Martin ; Kozáková, Hana (advisor) ; Prokešová, Ludmila (referee) ; Nevoral, Jiří (referee)
The main goal in reversing the allergy epidemic is the development of effective prophylactic strategies. Early life events, such as exposures to microbes, have a major influence on the development of balanced immune responses. Due to their ability to interact with host immune system and to modulate host immune responses probiotics, mainly bifidobacteria and lactobacilli have been used with some success in prevention of allergic disease. In order to be referred to as probiotic, bacterial strain has to undergo rigorous testing. We have selected three new Lactobacillus (L.) strains out of 24 human isolates according to their antagonistic activity against pathogenic bacteria, resistance to low pH and milieu of bile salts. Safety of these strains was proven upon intragastric administration to mice; moreover, we have shown their ability to shift cytokine Th1 - Th2 balance towards non-allergic Th1 response in isolated splenic cells. Allergen specific prophylaxis using probiotics as vehicles for mucosal delivery of recombinant allergen is an attractive concept for development of well-tolerated and effective allergy vaccines. We have shown that neonatal mono-colonization of germ-free mice with the L. plantarum NCIMB8826 strain producing the major birch pollen allergen Bet v 1 attenuates the development of...
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The Mechanism of Pathogenesis of Experimental Autoimmune Uveitis and Possilbilities of Their Regulation
Klímová, Aneta ; Heissigerová, Jarmila (advisor) ; Pitrová, Šárka (referee) ; Holáň, Vladimír (referee)
Introduction:Uveitis in an ocular inflammation affecting mostly people of working age. Uveitis is responsible for severe visual impairment despite of expanding new therapeutics. The animal models of uveitis were established, because the wide clinical variability of uveitis limits the studies in human medicine. The goal our project was to establish a reproducible model of experimental autoimmune uveitis in Czech Republic, and further on this model to observe the frequency of CD3+ and F4/80+ cells in retina, to assess the influence of microbial environment on intensity of intraocular inflammation and to test the therapeutical possibilities. Material and methods: The C57BL/6J mice were immunized by retinal antigen (IRBP 1-20, interphotoreceptor retinoid binding protein), enhanced by complete Freund's adjuvant and pertussis toxin and mild posterior autoimmune uveitis was induced. The mice were bred in conventional and germ-free (gnotobiotic) conditions. The uveitis intensity was evaluated in vivo biomicroscopically and post mortem histologically on hematoxylin eosin stained sections according to the standard protocol. The histological eye specimen were analyzed also by imunohistochemisty and by flow cytometry. Each experiment was performed for 35 days. The conventional mice with uveitis were treated...
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