The activation of p38alpha kinase mediates cell response to various extracellular factors including many interleukins and growth factors important for haematopoiesis. The role of p38alpha kinase was previously analysed in particular haematopoietic cells. In this study and for the first time, the role of p38alpha kinase in haematopoiesis was studied using a model of continuous haematopoietic development in pluripotent embryonic stem cells in vitro. The expression of transcripts associated with haematopoiesis and the potential for the formation of specific haematopoietic cell colonies were compared between wild-type and mutant p38alpha gene-depleted cells. The absence of p38alpha kinase led to the inhibition of hemangioblast formation during the first step of haematopoiesis. Later, during differentiation, due to the lack of p38alpha kinase, erythrocyte maturation was impaired. Mutant p38α-/- cells also exhibited decreased potential with respect to the expansion of granulocyte colony-forming units. This effect was reversed in the absence of erythropoietin as shown by colony-forming unit assay in media for colony-forming unit granulocytes/macrophages. p38alpha kinase thus plays an important role in the differentiation of common myeloid precursor cells into granulocyte lineages.
- Publikační typ
- časopisecké články MeSH
Massive toxic blooms of cyanobacteria represent a major threat to water supplies worldwide. Here, the biological activities of lipopolysaccharide (LPS) isolated from Microcystis aeruginosa, the most prominent cyanobacteria in water bloom, were studied. LPS was isolated from complex environmental water bloom samples dominated by M. aeruginosa, and from laboratory cultures of non-axenic as well as axenic M. aeruginosa strains PCC7806 and HAMBI/UHCC130. Employing human blood-based in vitro tests, the LPS isolated from complex water bloom revealed the priming of both major blood phagocyte population monocytes and polymorphonuclear leukocytes documented by the increased surface expression of CD11b and CD66b. This was accompanied by a water bloom LPS-mediated dose-dependent induction of tumor necrosis factor α, interleukin-1β, and interleukin-6 production. In accordance with its priming effects, water bloom LPS induced significant activation of p38 and ERK1/2 kinases, as well as NF-κB phosphorylation, in isolated polymorphonuclear leukocytes. Interestingly, the pro-inflammatory potential of LPS from the axenic strain of M. aeruginosa was not lower compared to that of LPS isolated from non-axenic strains. In contrast to the biological activity, water bloom LPS revealed almost twice higher pyrogenicity levels compared to Escherichia coli LPS, as analyzed by the PyroGene test. Moreover, LPS from the non-axenic culture exhibited higher endotoxin activity in comparison to LPS from axenic strains. Taking the above findings together, M. aeruginosa LPS can contribute to the health risks associated with contamination by complex water bloom mass.
- MeSH
- antigeny CD11b metabolismus MeSH
- CD antigeny metabolismus MeSH
- cytokiny krev MeSH
- eutrofizace MeSH
- GPI-vázané proteiny metabolismus MeSH
- kultivované buňky MeSH
- laboratoře MeSH
- leukocyty mononukleární účinky léků metabolismus MeSH
- lidé MeSH
- lipopolysacharidy toxicita MeSH
- Microcystis * MeSH
- molekuly buněčné adheze metabolismus MeSH
- přirozená imunita účinky léků MeSH
- pyrogeny toxicita MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The glycocalyx of the endothelium is an intravascular compartment that creates a barrier between circulating blood and the vessel wall. The glycocalyx is suggested to play an important role in numerous physiological processes including the regulation of vascular permeability, the prevention of the margination of blood cells to the vessel wall, and the transmission of shear stress. Various theoretical models and experimental approaches provide data about changes to the structure and functions of the glycocalyx under various types of inflammatory conditions. These alterations are suggested to promote inflammatory processes in vessels and contribute to the pathogenesis of number of diseases. In this review we summarize current knowledge about the modulation of the glycocalyx under inflammatory conditions and the consequences for the course of inflammation in vessels. The structure and functions of endothelial glycocalyx are briefly discussed in the context of methodological approaches regarding the determination of endothelial glycocalyx and the uncertainty and challenges involved in glycocalyx structure determination. In addition, the modulation of glycocalyx structure under inflammatory conditions and the possible consequences for pathogenesis of selected diseases and medical conditions (in particular, diabetes, atherosclerosis, ischemia/reperfusion, and sepsis) are summarized. Finally, therapeutic strategies to ameliorate glycocalyx dysfunction suggested by various authors are discussed.
- MeSH
- cévní endotel metabolismus patologie MeSH
- glykokalyx metabolismus patologie MeSH
- lidé MeSH
- zánět metabolismus patologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Crohnova nemoc je komplexní chronické zánětlivé onemocnění trávicí soustavy, na jehož patogenezi se podílí celá řada faktorů. Incidence Crohnovy nemoci v posledních letech zaznamenala poměrně prudký nárůst, a přestože je tato nemoc známa již delší dobu, její příčinu se doposud nepodařilo odhalit. Nové poznatky v patogenezi onemocnění přinesly studie zabývající se genetickou podstatou Crohnovy nemoci. Výsledky těchto studií poukazují na selhání mechanizmů symbiózy střevní mikroflóry a střevního slizničního imunitního systému. Zdá se, že Crohnova nemoc vzniká nepřiměřenou reakcí imunitního systému na střevní mikroflóru u geneticky predisponovaných jedinců. S Crohnovou nemocí byla asociována celá řada genů. Mnohé z nich souvisejí s funkcí nespecifické imunitní odpovědi, jejíž nedostatky jsou v dnešní době považovány za klíčové v patogenezi Crohnovy nemoci. Cílem tohoto přehledového článku je shrnout nové poznatky v patogenezi Crohnovy nemoci na úrovni polymorfizmů v genech NOD2, ATG16L1 a v genech signální dráhy IL23-Th17-lymfocyty a zmínit další směry výzkumu v problematice tohoto onemocnění.
Crohn's disease is a complex chronic inflammatory disease of the gastrointestinal tract with multifactorial pathogenesis. Over the recent years, there has been rather a sharp increase in the incidence of Crohn's disease and, even though this disease had been known for some time, the cause remains unknown. Studies exploring genetic basis of Crohn's disease have provided new knowledge of the pathogenesis of this disease, suggesting that this may be associated with a failure of mechanisms behind symbiosis of gut microflora and intestinal mucosal immune system. Crohn's disease seems to be caused by inadequate immune response to intestinal flora in genetically predisposed individuals. Crohn's disease has been linked to a number of genes. Many of them are related to the modulation of non-specific immune response, defects of which are considered to be key in Crohn's disease pathogenesis. The aim of this review paper is to summarize the new knowledge on the pathogenesis of Crohn's disease at the level of polymorphisms of the NOD2, ATG16L1 genes and the IL23-Th17-lymfocytes signalling pathway genes and to consider further research directions in this disease.
- Klíčová slova
- patogeneze, NOD2, ATG16L1, IL23-Th17-lymfocyty,
- MeSH
- Crohnova nemoc etiologie genetika patofyziologie MeSH
- lidé MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
