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Role of Fibroblasts in Regulation of Wound Healing
Zavaďáková, Anna ; Vištejnová, Lucie (advisor) ; Buchtová, Marcela (referee) ; Krulová, Magdaléna (referee)
Dermal fibroblasts participate actively in the regulation of wound healing process. They migrate and proliferate during the proliferative phase into the wound site and respond to signals from damaged tissue by secretion of a various pro-inflammatory molecules (e.g. interleukins IL6 and IL8) and extracellular matrix components (e.g. collagen type I, hyaluronan, fibronectin). The disruption of the balance and timing of synthesis and degradation of these molecules can lead to the transition of normal to abnormal non-healing process. Several stress factors act simultaneously in this type of wounds - impaired nutrition supply, inflammation, bacterial contamination, oxidative stress etc. However, the latest in vitro research of dermal fibroblasts in wound healing apply most often only one stress factor. This thesis deals with the response of dermal fibroblasts to the wound conditions. For the first time, a comprehensive study of the functional response of the cells to the two key wound stress factors is described in 2D culture and 3D self-made collagen hydrogel culture. In the first part of the thesis response of dermal fibroblasts to the wound conditions applying two stress factors - low nutrition (2% FBS) and inflammation simulated by bacterial lipopolysaccharide (LPS) - is characterized. The...
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Cytokine expression in regressive melanoma on porcine MeLiM model
Miltrová, Veronika ; Skalníková, Helena (advisor) ; Krulová, Magdaléna (referee)
Cutaneous melanoma is a very aggressive cancer with increasing incidence. It originates from transformed pigmented skin cells (melanocytes). The main risk factor for melanoma development is exposure to UV light and repeated sunburns. In approximately 10 % of cases, melanoma occurs on hereditary basis. Patients with cutaneous melanoma diagnosed in early stages have very good prognosis, with surgical resection of the primary tumour being mostly sufficient for treatment. In contrast, the advanced melanoma stages with metastases are often progressive and refractory to conventional therapies. Cutaneous melanoma is referred to as an immunogenic tumour that is frequently infiltrated by cells of the immune system. Tumours with immune cell infiltration show better prognosis. Spontaneous regression may occur. Over the last few years, progress has been made in the treatment of melanoma using checkpoints molecules (anti-CTLA-4 and anti-PD-1) to activate patients own immune system to recognize tumour lesions. In the tumour microenvironment, cytokines play an important role, enabling communication between cells and regulation of cell proliferation and migration and thus the tumour development. Cytokines (IL-2, IFNα) can be used in adjuvant therapy of melanoma. This work analysed levels of expressed cytokines in...
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Autophagy in adipose tissue
Somova, Veronika ; Krulová, Magdaléna (advisor) ; Zouhar, Petr (referee)
Autophagy is an essential mechanism of recycling, which represents a path leading to utilization and reorganization of intracellular components (nutrients, organelles, etc). Recent studies on adipose tissue have shown, that autophagy plays crucial role in differentiation of the adipocytes precursors and in phenotypic tissue transformations. The aim of this thesis is to summarize the characteristics of autophagy in terms of various adipose tissues as well as to present the regulation of autophagy as a potentially useful in therapy focused on obesity treatment. However, with the regulation of autophagy, there are risks that will also be considered in the present thesis. Keywords: autophagy, adipose tissue, therapy
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The effect of cold adaptation on the immune system
Vašek, Daniel ; Krulová, Magdaléna (advisor) ; Filipp, Dominik (referee)
Maintaining energy homeostasis at reduced temperatures is essential for the survival of the organisms. In this diploma thesis, we determined the impact of cold stress and cold adaptation on the rat immune system. A number of different factors participate at the process of thermoregulation, but the adrenergic signalling plays a crucial role. The binding of norepinephrine to β-adrenergic receptors leads to the formation of brown adipose tissue, which is necessary for non-shivering thermogenesis, as well as for energy balance. Bioactive products of adipocytes subsequently modulate the immune system, this process is significantly influenced by signalling of nerve cells. In order to understand neuro-immune interaction during the cold adaptation, we monitored changes in immune cell populations and the production of soluble products in rats treated with specific inhibitors of β-adrenergic receptors. Relationship between the immune and nervous system seems to be very important in many biological processes. Deciphering basic mechanisms of the influence of cold adaptation on immune cells can therefore explain other clinically relevant topics, such as treatment of obesity. Key words: immune system, cold adaptation, norepinephrine, adrenergic receptor, cytokines, brown adipose tissue, non-shivering thermogenesis
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Role of enteric alpha-defensins in inflammatory bowel disease
Jakubec, Martin ; Filipp, Dominik (advisor) ; Krulová, Magdaléna (referee)
Human intestine represents an essential immune organ that creates the largest interface between our immune system and microbiota from the environment. Considerable parts of the intestine are often severely damaged during Crohn's disease (CD), chronic inflammatory condition with a rising incidence in the western countries. Outbreak of intestinal inflammation is associated with the loss of intestinal homeostasis, co-manifested as a microbial dysbiosis. It is yet unknown whether this bacterial dysbiosis is the cause of intestinal inflammation, or rather it's consequence. In healthy individuals, the homeostatic relationship is greatly influenced by Paneth cells (PC). These cells produce and secrete a wide variety of antimicrobial proteins and peptides, such as enteric α-defensins, that constantly shape the composition of intestinal microbiota. Unsurprisingly, defects in PC's functioning have been linked to the development of CD. Here, we build on our previously published data which showed that a defect in immune central tolerance is the cause of PC depletion. Due to phenotypic and functional resemblance, we hypothesized that such depletion of PCs could constitute a trigger for the development of CD in at least a subset of these patients. This thesis represents a case control study of newly diagnosed...
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Genetic regulation of Leishmania infection
Sohrabi, Yahya ; Lipoldová, Marie (advisor) ; Krulová, Magdaléna (referee) ; Kolářová, Iva (referee)
6 Abstract Leishmaniasis is a neglected tropical disease, which belongs to the top health problems because it is endemic in 98 countries in Asia, Africa, the Americas and the Mediterranean region, and is gradually expanding to new areas, including Central Europe and USA. Clinical manifestations of leishmaniasis include a diverse range of forms, ranging from non-lethal cutaneous leishmaniasis to potentially lethal visceral leishmaniasis. Asymptomatic cases are known to exist in endemic areas. Different species of Leishmania induce distinct symptoms, but even the patients infected by the same species develop different symptoms and may respond differently to the treatment. Thus, one of the challenges is to explain the observed variability of leishmaniasis that cannot be attributed to the currently known factors. To find novel regulatory factors of the disease we tested molecules that were shown to play role in other infections and mapped loci controlling parasite load after L. major infection. We also determined genetic control of survival after infection with tick-borne encephalitis virus (TBEV) in order to establish whether there are common elements in response to L. major and TBEV. Interferon-induced GTPases (guanylate-binding proteins, GBPs) play an important role in inflammasome activation and mediate...
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Study of the effect of mesenchymal stem cells in combination with immunosuppressive therapy on inflammatory response in in vivo model
Jabůrek, Filip ; Krulová, Magdaléna (advisor) ; Brdička, Tomáš (referee)
Immunosuppressive drugs have been used for many years for the treatment of autoimmune diseases and post-transplantation treatment. While these drugs have a lot of advantages, they also show several undesirable side effects. The most common side effects are higher blood pressure, lowered renal function and susceptibility to infections. Therefore, in recent years there has been a demand for other medical approaches that do not exhibit the above-mentioned adverse effects. Among one of the newly tested approaches is the application of mesenchymal stem cells (MSCs), which possess several advantages such as immunomodulatory abilities, safety and relatively easy isolation, however, stem cell use alone has not yet provided sufficiently strong immunomodulation. Only a small part of research of MSCs is focused on their use in the combination with immunosuppressive therapy. Therefore, in my thesis I focused on the model which allows to reduce the dose of immunosuppressive drugs in the combination with MSCs. Combined therapy is more advantageous than both monotherapies thanks to lower dosages of these drugs used. It enables to decrease negative side effects of immunosuppressive drugs, when combined with MSCs to provide sufficient immunomodulation in comparison to classical therapy. The aim of my work was to...
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The effect of progesteron administration on T regulatory cells in relation to preterm deliveries
Škvorová, Anna ; Hrdý, Jiří (advisor) ; Krulová, Magdaléna (referee)
During pregnancy, the maternal organism has to cope with the presence of foreign paternal antigens, allow and support the development of a semialogenic fetus, while maintaining its defense against pathogens. This condition is achieved by a dynamic balance of complex immuno-endocrine interactions. A number of cells with specific properties contributes to the tolerogenic setting during pregnancy. Very important role plays the population of T regulatory lymphocytes (Treg). Treg levels increase physiologically during pregnancy and their decline is associated with term and preterm labor. Premature birth is a serious socio-economic problem, affecting around 10 % of births worldwide. In the case of increased risk of premature labor, progesterone administration has been successfully used in clinical practice. One hypothesis says that progesterone induces an increase in Treg population and delays premature labor in this way. The aim of the thesis was to monitor the effect of progesterone therapy in vivo on the amount and functional properties of CD4+ CD25+ FoxP3+ Helios+/- Treg and to verify whether long-term vaginal administration of progesterone positively correlates with an increase in Treg counts. Another goal was to determine whether progesterone promotes Treg generation and the production of...
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Effect of stress hormones on mesenchymal stem cells
Karásková, Eva ; Krulová, Magdaléna (advisor) ; Hejnová, Lucie (referee)
Mesenchymal stem cells (MSCs) are multipotent cells with the capacity to differentiate into cell lineages such as osteoblasts, adipocytes and chondrocytes. They maintain homeostasis in organism and contribute to wound healing and tissue regeneration. Usually, they are isolated from bone marrow or adipose tissue and they are primarily studied in regenerative medicine. Stress reaction is neurohumoral preparation for "fight or flight", that occurs in response to physical or mental stresssors. However, chronic stress has a negative impact on organism; it causes gradual exhaustion and damage in the whole body. Main hypothesis of this study is that stress hormones and neurotransmitters affect MSCs, which subsequently results in disturbed homeostasis and integrity of organism, delayed wound healing and attenuated tissue regeneration. Stress hormones influence quality and function of MSCs, especially their capabilities of differentiation, migration to wounded tissue and production of bioactive molecules. Key words: mesenchymal stem cells (MSCs), catecholamines, hormones, dopamine, nervous system, stress
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