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The role of TNF-alpha and IL-10 in cardioprotective effect of chronic hypoxia
Chytilová, Anna ; Bezouška, Karel (advisor) ; Hloušková, Patricie (referee)
The aim of the present study was to find out whether adaption to chronic hypoxia affects the expresion of TNF-α and IL-10 in rat myocardium. TNF-α is a proinflammatory cytokine, which amplifies inflammatory reaction, while IL-10 has opposite antiinflammatory effect. We also measured concentration of nitrotyrosine as a marker of nitrosative stress. We used male Wistar rats divided into four groups: 1) normoxic controls; 2) exposed to continous normobaric hypoxia (10% O2) for three days or 3) for three weeks and 4) exposed to intermittent normobaric hypoxia (10% O2) for three weeks with one hour daily reoxygenation. Cytosolic and membrane proteins (cytosolic and particulate fractions) were obtained from the left ventricle, right ventricle and interventricular septum. Concentrations of TNF-α and IL-10 in both fractions were measured by ELISA. Continous hypoxia increased TNF-α production in particulate fractions from all ventricular parts and decreased the ratio of IL-10/TNF-α in particulate and cytosolic fractions. Intermittent hypoxia redistributed TNF-α from cytosol into the particulate fraction and prevented the drop of IL-10/TNF-α ratio in the cytosolic fraction. The highest concentration of nitrotyrosine was found in the particulate fraction from the right ventricle after three days of hypoxia....
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Comparison of Immune System of Newborns and Adults
Dusilová, Adéla ; Zajícová, Alena (referee) ; Hrdý, Jiří (advisor)
In general, it is possible to characterize neonatal immune system (IS) as immature in comparison to adult IS. From a clinical point of view, newborns show an increased susceptibility to infections. Breastfeeding can contribute to the descent incidence of illnesses, because it supplies the intestinal mucosal system with antibodies of the mother`s origin, important nutrients and other immunoregulatory components. Breast milk compensates decreased newborn's capacity to produce immunoglobulins- especially IgA, that concentration reaches adult levels in two years, but even later (to the pubescent period). Other classes of antibodies are found in cord blood only sporadically except IgG, which is transferred transplacentary. Reduced ability of B lymphocytes to produce antibodies is caused by insufficient expression of surface costimulatory signals of Th2 cells. T lymphocytes are not able to react properly to low doses of stimulators (polyclonal activators - phytoid lectins: ConA or PHA), which bind to T cell receptors in complex with CD3 and proliferate in a response to anti-CD3 monoclonal antibodies. Most of the cord blood T lymphocytes display "naive" phenotype CD45RA. During intrauterine development, neonatal IS is in contact with mother IS and because a pro-inflammatory Th1 response could lead to...
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Origins of vertebrate hematiopoiesis
Svoboda, Ondřej ; Bartůněk, Petr (advisor) ; Divoký, Vladimír (referee) ; Živný, Jan (referee)
(ENGLISH) Hematopoiesis is dependent on the actions of hematopoietic stem cells (HSCs). This process is tightly controlled through a complex array of extrinsic and intrinsic factors. Even though the hematopoiesis seems to be well conserved across the disparate vertebrate animals, erythroid and thrombocytic differentiation have changed during the evolution of mammals. Specifically, adult mammalian red blood cells have the unique feature of being enucleated, and mammalian thrombocytes are not individual cells, but fragments of megakaryocytes, instead. It is likely that these enhancements provided a survival advantage to early mammalian species; however, they also bring up the question of evolutionary origin of these cells that studied using zebrafish (Danio rerio) model. First, it was necessary to generate a toolbox of a recombinant cytokines and optimized culture media that allowed us to manipulate zebrafish hematopoietic cells ex vivo in liquid and clonal cultures. Interestingly, teleost species underwent an extra duplication event during their evolution and as a result, two copies (paralogs) of some of the genes are present in zebrafish. This was also the case for majority of the cytokines from our toolbox and here, we provide functional characterization of these paralogs. Strikingly, our results...
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The effect of tick´s serpin IRS-2 on dendritic cells activated by TLR4 ligand
POSPÍŠILOVÁ, Šárka
IRS-2 is the inhibitor of serine proteases from the Ixodes ricinus tick. My task in this thesis was to find out the effect of the IRS-2 on dendritic cells activated by TLR4 ligand or by Borrelia afzelii. This effect was studied on several levels. I focused on the cytokine production, the expression of costimulatory molecules and cell signaling pathways. The results show that the IRS-2 may inhibit the expression of costimulatory molecules CD-80 a CD-86 on the cell surface, but this finding needs to be confirmed again. The production of cytokines was not affected by the IRS-2. The effect of the IRS-2 on the activity of p38, Erk1/2 nor NF-?B in LPS stimulated cells vas not observed. The fosforylation of STAT 3 in cells activated by the B. afzelii was lowered by the IRS-2.
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