|
|
Anti-inflammatory effects of ursodeoxycholyl lysophosphatidylethanolamide on THP-1 human macrophages via Toll-like receptor 4
Horvátová, Alžbeta ; Pávek, Petr (advisor) ; Nachtigal, Petr (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Alžbeta Horvátová Supervisor: prof. PharmDr. Petr Pávek PhD. Title of diploma thesis: Anti-inflammatory effects of ursodeoxycholyl lysophosphatidylethanolamide on THP-1 human macrophages via Toll-like receptor 4 Nonalcoholic steatohepatitis (NASH) became the most common liver disease in developed countries. It is well-known that the level of protectant phosphatidylcholine (PC) is decreased in NASH. The bile acid-phospholipid conjugate ursodeoxycholyl lysophosphatidylethanolamide (UDCA-LPE) was designed in order to specifically deliver PC to hepatocytes. However, previous studies have proved that UDCA-LPE possesses its proper hepatoprotectant capacity and exhibits anti-apoptotic, anti-inflammatory, anti-fibrotic properties and also improved steatosis and hyperlipidaemia in various models in vivo. These effects may be mediated secondary through modulation of immune system. Therefore, in order to dissect if UDCA-LPE directly influences immune cells in vitro, release of pro-inflammatory cytokines TNFα, IL-6 and IL-1β in LPS-induced THP-1-derived human macrophages was measured by ELISA. Moreover, effects of UDCA-LPE on MAPK signalling pathways and nuclear translocation of NFκB were...
|
|
|
Biological mechanisms of function of the HIC1 tumor suppressor
Hlavatá, Adéla ; Kořínek, Vladimír (advisor) ; Macůrková, Marie (referee)
The tumor suppressor gene HIC1 encodes a BTB/POZ transcription repressor. Its promotor is frequently hypermetylated in large numbers of tumors. HIC1 also functions as a negative modulator of the Wnt signalling pathway, which fundamentally participates in regulation of stem cell renewal of the intestinal epithelium. Thanks to its structural features the intestinal epithelium represents a convenient model tissue to study stem cells and their pathology. To overcome the embryonic lethality of the complete Hic1 "knock-out" the conditional deletion of the gene in adult mouse tissue was chosen to evaluate the Hic1 biological aktivity. By the chip expression analysis of mouse embryonic fibroblasts we discovered a number of new target genes of Hic1, the most interesting of them - in respect to cancer - we considered the Toll-like receptor 2 gene. The expression of Hic1 target genes is likely to be co-regulated by p53 although the direct regulation wasn't proved. Hic1 affects the proportion of the differentiated intestinal epithelial cells types possibly via regulation of Atoh1. After conditional deletion of Hic1 in the intestinal epithelium we observed and quantitatively confirmed a significant increase of the amounts of goblet cells. We concluded that Hic1 affects differentiation pathways in intestinal...
|
|
|
Cellular signaling pathways engaged in the entrainment of mammalian biological clock
Červená, Kateřina ; Bendová, Zdeňka (advisor) ; Svobodová, Irena (referee)
The mammalian biological clock is based on endogenous rhythmic oscillations of the so-called clock genes which affects the timing of the external manifestations, such as rhythmic alternations of sleep and activity. This endogenous mechanism, of which the innate period slightly deviates from the solar time, can be adjusted by various external synchronizers to the exact 24 hour period. This thesis is focused on the influence of the most prominent synchronizer, the sunlight, on the molecular basis of changes in the dynamics of internal mechanism of the oscillations in the main mammalian circadian pacemaker, the suprachiasmatic nuclei of the hypothalamus. There are numerous studies which have demonstrated the effect of various cellular signaling pathways on changes of circadian rhythms. The most common methods of assessing the oscillation phase changes, however, measure changes in output rhythms that may not always reflect the changes in the molecular mechanism itself. The aim is to evaluate which components of signaling pathways have provably shown to affect the dynamics of the rhythmic expression of clock genes.
|
guest ::
