Intestinal inflammation
Dotaz
Zobrazit nápovědu
Falk symposium ; 158
Přeruš. str. : il., tab. ; 21 cm
- MeSH
- kolorektální nádory terapie MeSH
- nemoci střev terapie MeSH
- Publikační typ
- abstrakt z konference MeSH
- sborníky MeSH
- Konspekt
- Patologie. Klinická medicína
- NLK Obory
- gastroenterologie
- onkologie
Scandinavian journal of gastroenterology ; Supplement Vol. 29. 203
[1st ed.] 68 s. : obr., tab., grafy ; 28 cm
- MeSH
- břicho ultrasonografie radiografie MeSH
- diagnostické techniky kardiovaskulární MeSH
- diagnostické zobrazování MeSH
- idiopatické střevní záněty diagnóza MeSH
- sepse MeSH
- Publikační typ
- kongresy MeSH
- sborníky MeSH
- Konspekt
- Patologie. Klinická medicína
- NLK Obory
- gastroenterologie
- chemie, klinická chemie
Biologická terapie představuje jeden z největších pokroků současné klinické gastroenterologie. Její podání je cíleno především na neutralizaci klíčového prozánětlivého cytokinu TNF-α (tumor nekrotizující faktor α). Cílem biologické léčby je dosažení remise onemocnění, zabránění vzniku komplikací, snížení nutnosti chirurgických výkonů a zlepšení kvality života pacientů s Crohnovou chorobou a ulcerózní kolitidou. V klinické praxi se využívají dvě molekuly s podobným mechanismem účinku (infliximab a adalimumab), před branami klinické praxe je třetí látka (certolizumab). Kontrolované klinické zkoušky ukázaly, že všechny tři látky jsou velmi účinné v léčbě středně a vysoce aktivní Crohnovy nemoci. Jejich nepřímé srovnání vykazuje podobnou efektivitu. Asi 30 % nemocných přejde do remise po zahájení biologické terapie, takže je možné ukončit léčbu kortikoidy a významně zlepšit kvalitu života. U 30 % nemocných dojde ke zlepšení stavu a je nutné trvalé podávání léčiva, u 30 % pacientů terapie od počátku nebo v průběhu opakovaného podávání postupně ztratí efekt. Novější látky (adalimumab, certolizumab) se podávají subkutánně a mají výhodu minimálních alergických reakcí. Infliximab je používán v klinické praxi již devět let, a proto jsou s léčbou tímto přípravkem nejrozsáhlejší zkušenosti. Je velmi účinný také u nemocných s ulcerózní kolitidou, navíc ho lze využít jako záchrannou léčbu u pacientů s hrozícím chirurgickým výkonem pro velmi těžký průběh nemoci. Indikace k zahájení biologické terapie je založena na znalosti předcházejícího průběhu nemoci a selhání konvenčních léčebných schémat. V budoucnosti je možné uvažovat o využití genetických nebo proteomických parametrů, které by umožnily zahájit léčbu v časných fázích onemocnění.
The biological treatment is one of the greatest advances in the current clinical gastroenterology. It is primarily focused on neutralization of the key anti-inflammatory cytokine TNF- α (tumor necrosis factor α ). The objectives of the biological treatment are to achieve disease remission, to prevent complications, to reduce the need for surgery and to improve quality of life of patients with Crohn’s disease and ulcerative colitis. Two molecules with a similar mechanism of activity (infliximab and adalimumab) are used in clinical practice and a third one (certolizumab) will soon be available for clinical use. In controlled clinical trials, all three drugs have proven highly effective in the treatment of moderate to highly active Crohn’s disease. An indirect comparison has shown their similar efficacy. About 30 % of patients achieve remission after the institution of biological treatment, and as a result, corticosteroids can be withdrawn with subsequent considerable improvement of quality of life. The condition improves in 30 % of patients who are given the drug on a permanent basis and in 30 % of patients, the treatment is ineffective from the very beginning or progressively becomes so. The more recent drugs (adalimumab, certolizumab) are given subcutaneously and unlike infliximab have the advantage of causing minimal allergy reactions. Infliximab has been in clinical use for nine years and that is why the greatest experience has been gained with this drug. It is highly effective also in patients with ulcerative colitis. Morover, it can be used as rescue therapy in patients who would otherwise need surgery for a very serious course of the disease. Indication for the institution of biological treatment is based on knowledge of the previous course of disease and failure of the conventional therapeutic schemes. In the future, some genetic and/or proteomic parameters may prove of relevance to the institution of the treatment in early phases of the disease.
- MeSH
- biologická terapie klasifikace trendy využití MeSH
- Crohnova nemoc imunologie terapie MeSH
- dítě MeSH
- dospělí MeSH
- idiopatické střevní záněty terapie MeSH
- lidé MeSH
- TNF-alfa farmakologie klasifikace terapeutické užití MeSH
- ulcerózní kolitida imunologie terapie MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé MeSH
The intestine hosts the largest immune system and peripheral nervous system in the human body. The gut‒brain axis orchestrates communication between the central and enteric nervous systems, playing a pivotal role in regulating overall body function and intestinal homeostasis. Here, using a human three-dimensional in vitro culture model, we investigated the effects of serotonin, a neuromodulator produced in the gut, on immune cell and intestinal tissue interactions. Serotonin attenuated the tumor necrosis factor-induced proinflammatory response, mostly by affecting the expression of chemokines. Serotonin affected the phenotype and distribution of tissue-migrating monocytes, without direct contact with the cells, by remodeling the intestinal tissue. Collectively, our results show that serotonin plays a crucial role in communication among gut-brain axis components and regulates monocyte migration and plasticity, thereby contributing to gut homeostasis and the progression of inflammation. In vivo studies focused on the role of neuromodulators in gut inflammation have shown controversial results, highlighting the importance of human experimental models. Moreover, our results emphasize the importance of human health research in human cell-based models and suggest that the serotonin signaling pathway is a new therapeutic target for inflammatory bowel disease.
- Klíčová slova
- MESALAZIN, PENTASA, SALOFALK, ASACOL, DIPENTUM,
- MeSH
- Crohnova nemoc farmakoterapie MeSH
- proktokolitida farmakoterapie MeSH
- salicylany aplikace a dávkování terapeutické užití MeSH
- sulfasalazin MeSH
- Publikační typ
- přehledy MeSH
- srovnávací studie MeSH
Aflatoxin B1 is a mycotoxin that widely exists in feed and has a great impact on human and animal health. This study aimed to examine whether Bacillus amyloliquefaciens B10 protected against aflatoxin B1-induced cecal inflammation in mice. It was found that Bacillus amyloliquefaciens B10 could significantly improve the effects of AFB1 on body weight and intestinal inflammation of mice and enhance the expression of tight-junction protein. Compared with the CON group, the combination of AFB1 and B10 significantly increased the abundance of Actinobacteria and Bacilli in a collaborative manner, and significantly reduced the abundance of Ruminococcae, Lactobacillaceae and Clostridia. Meanwhile, the results showed that the abundance of Bacterides and Bacterdia in AFB1 + B10 group was significantly lower than that of AFB1 group, and the Firmicutes increased significantly. Bacillus amyloliquefaciens B10 can be used as a feed additive and alleviate cecal inflammation induced by AFB1 in mice by regulating intestinal flora.
The effect of glucocorticoids is controlled at the pre-receptor level by the activity of 11beta-hydroxysteroid dehydrogenase (11HSD). The isoform 11HSD1 is an NADP+ -dependent oxidoreductase, usually reductase, that amplifies the action of glucocorticoids due to reduction of the biologically inactive 11-oxo derivatives cortisone and 11-dehydrocorticosterone to cortisol and corticosterone. The NAD+ -dependent isoform (11HSD2) is an oxidase that restrains the effect of hormones due to 11beta-oxidation of cortisol and corticosterone to their 11-oxo derivatives. Although the immunosuppressive and anti-inflammatory effects of glucocorticoids are well known, the relationship between inflammation and local metabolism of glucocorticoids is not well understood. In this study, we demonstrated that colitis induced by dextran sulfate sodium modulates colonic 11HSD1. Experimentally induced intestinal inflammation stimulated colonic NADP+ -dependent but not NAD+ -dependent 11HSD activity. Colonic 11HSD1 mRNA was increased, whereas 11HSD2 mRNA was not changed. Additional parallel studies revealed a similar pattern of 11HSD1 mRNA induction in mesenteric lymph nodes and intestinal intraepithelial lymphocytes, but not in spleen and peritoneal macrophages. These data suggest that inflammation modulates local metabolism of glucocorticoid and support the notion that pre-receptor regulation of endogenous corticosteroids might play a role in inflammatory processes.
- MeSH
- 11-beta-hydroxysteroiddehydrogenasy genetika metabolismus MeSH
- aktivace enzymů MeSH
- kolitida * enzymologie MeSH
- kolon * enzymologie MeSH
- messenger RNA * analýza MeSH
- modely u zvířat MeSH
- myši inbrední BALB C MeSH
- myši MeSH
- polymerázová řetězová reakce s reverzní transkripcí MeSH
- síran dextranu MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- práce podpořená grantem MeSH
The gut is the biggest immune organ in the body that encloses commensal microbiota which aids in food digestion. Paneth cells, positioned at the frontline of host-microbiota interphase, can modulate the composition of microbiota. Paneth cells achieve this via the delivery of microbicidal substances, among which enteric α-defensins play the primary role. If microbiota is dysregulated, it can impact the function of the local mucosal immune system. Importantly, this system is also exposed to an enormous number of antigens which are derived from the gut-resident microbiota and processed food, and may potentially trigger undesirable local inflammatory responses. To understand the intricate regulations and liaisons between Paneth cells, microbiota and the immune system in this intestinal-specific setting, one must consider their mode of interaction in a wider context of regulatory processes which impose immune tolerance not only to self, but also to microbiota and food-derived antigens. These include, but are not limited to, tolerogenic mechanisms of central tolerance in the thymus and peripheral tolerance in the secondary lymphoid organs, and the intestine itself. Defects in these processes can compromise homeostasis in the intestinal mucosal immunity. In this review, which is focused on tolerance to intestinal antigens and its relevance for the pathogenesis of gut immune diseases, we provide an outline of such multilayered immune control mechanisms and highlight functional links that underpin their cooperative nature.
- MeSH
- alfa-defensiny biosyntéza imunologie farmakologie MeSH
- centrální tolerance MeSH
- dysbióza imunologie mikrobiologie prevence a kontrola MeSH
- exprese genu imunologie MeSH
- gastrointestinální trakt účinky léků imunologie mikrobiologie MeSH
- homeostáza imunologie MeSH
- lidé MeSH
- Panethovy buňky účinky léků imunologie mikrobiologie MeSH
- periferní tolerance * MeSH
- regulační T-lymfocyty imunologie mikrobiologie MeSH
- slizniční imunita účinky léků MeSH
- střevní mikroflóra imunologie MeSH
- symbióza imunologie MeSH
- zánět MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Circulating extracellular DNA (ecDNA) is known to worsen the outcome of many diseases. ecDNA released from neutrophils during infection or inflammation is present in the form of neutrophil extracellular traps (NETs). It has been shown that higher ecDNA concentration occurs in a number of inflammatory diseases including inflammatory bowel disease (IBD). Enzymes such as peptidyl arginine deiminases (PADs) are crucial for NET formation. We sought to describe the dynamics of ecDNA concentrations and fragmentation, along with NETosis during a mouse model of chemically induced colitis. Plasma ecDNA concentration was highest on day seven of dextran sulfate sodium (DSS) intake and the increase was time-dependent. This increase correlated with the percentage of cells undergoing NETosis and other markers of disease activity. Relative proportion of nuclear ecDNA increased towards more severe colitis; however, absolute amount decreased. In colon explant medium, the highest concentration of ecDNA was on day three of DSS consumption. Early administration of PAD4 inhibitors did not alleviate disease activity, but lowered the ecDNA concentration. These results uncover the biological characteristics of ecDNA in IBD and support the role of ecDNA in intestinal inflammation. The therapeutic intervention aimed at NETs and/or nuclear ecDNA has yet to be fully investigated.
- MeSH
- biologické markery metabolismus MeSH
- deoxyribonukleasy metabolismus MeSH
- DNA krev metabolismus MeSH
- endoskopie MeSH
- extracelulární pasti účinky léků metabolismus MeSH
- extracelulární prostor metabolismus MeSH
- kolitida krev chemicky indukované patologie MeSH
- mitochondriální DNA krev MeSH
- myši inbrední C57BL MeSH
- ornithin analogy a deriváty farmakologie MeSH
- peptidylarginindeiminasa typu 4 metabolismus MeSH
- síran dextranu MeSH
- streptonigrin farmakologie MeSH
- střeva účinky léků patologie MeSH
- střevní sliznice účinky léků patologie MeSH
- stupeň závažnosti nemoci MeSH
- zánět krev patologie MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
112 listů : ilustrace, tabulky ; 30 cm + autoreferát stejného názvu o 14 stranách
