V posledních letech dochází k průlomovým poznatkům týkajícím se ultra-/struktury a funkce intestinální epiteliální bariéry. Současně se ukazuje, jak významná je evolučně získaná schopnost makroorganizmu dynamicky koordinovat spolupráci s komplexním kolonizujícím mikrobiálním ekosystémem pro udržení zdraví a k prevenci onemocnění. K porušení intestinální epiteliální bariéry může docházet při akutních i chronických chorobných stavech primárně infekční i neinfekční etiologie. Předkládaný přehled shrnuje aktuální znalosti o struktuře a funkci intestinální epiteliální bariéry.

In recent years, there has been a revolutionary outbreak of our knowledge about ultra-/structure and function of the intestinal epithelial barrier. During evolution acquisited ability of the macroorganism to dynamically coordinate the interaction with the complexe colonizing microbial ecosystem has been recently shown to be crucial in the health and in the illness-prevention. As acute as chronic pathological conditions, primarilly infectious or non-infectious, may lead to disruption of the intestinal epithelial barrier. The presented overview summarises actual knowledge about structure and function of the intestinal epithelial barrier. Key words: intestinal epithelial barrier – tight junctions – infection The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE „uniform requirements“ for biomedical papers. Submitted: 8. 8. 2013 Accepted: 18. 11. 2013

• Klíčová slova
• intestinální epiteliální bariéra, těsná spojení,
• MeSH
• epitelové buňky fyziologie   metabolismus   MeSH
• lidé MeSH
• slizniční imunita * MeSH
• střevní sliznice * fyziologie   imunologie   metabolismus   MeSH
• těsný spoj * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH
• přehledy MeSH

Since the 1960s, more than 350,000 new chemicals have been introduced into the lives of humans and domestic animals. Many of them have become part of modern life and some are affecting nature as pollutants. Yet, our comprehension of their potential health risks for both humans and animals remains partial. The "epithelial barrier theory" suggests that genetic predisposition and exposure to diverse factors damaging the epithelial barriers contribute to the emergence of allergic and autoimmune conditions. Impaired epithelial barriers, microbial dysbiosis, and tissue inflammation have been observed in a high number of mucosal inflammatory, autoimmune and neuropsychiatric diseases, many of which showed increased prevalence in the last decades. Pets, especially cats and dogs, share living spaces with humans and are exposed to household cleaners, personal care products, air pollutants, and microplastics. The utilisation of cosmetic products and food additives for pets is on the rise, unfortunately, accompanied by less rigorous safety regulations than those governing human products. In this review, we explore the implications of disruptions in epithelial barriers on the well-being of companion animals, drawing comparisons with humans, and endeavour to elucidate the spectrum of diseases that afflict them. In addition, future research areas with the interconnectedness of human, animal, and environmental well-being are highlighted in line with the "One Health" concept.

• MeSH
• domácí zvířata * imunologie   MeSH
• epitel imunologie   MeSH
• kočky MeSH
• lidé MeSH
• psi MeSH
• vystavení vlivu životního prostředí škodlivé účinky   MeSH
• zvířata MeSH
• Check Tag
• kočky MeSH
• lidé MeSH
• psi MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

We aimed to investigate the effects of brain-derived neurotrophic factor (BDNF) on apoptosis of intestinal epithelial cells (IECs) and alterations of intestinal barrier integrity using BDNF knock-out mice model. Colonic tissues from BDNF(+/+) mice and BDNF(+/-) mice were prepared for this study. The integrity of colonic mucosa was evaluated by measuring trans-mucosa electrical resistance and tissue conductance in Ussing chamber. The colonic epithelial structure was analyzed by transmission electron microscopy. Apoptosis involvement was determined with TUNEL staining, active caspase-3 immunostaining and Western blotting for the protein expression of active caspase-3, Bax and Bcl-2. The expression levels and distribution of tight junction proteins were evaluated by immunohistochemistry or Western blots. Compared with BDNF(+/+) mice, BDNF(+/-) mice displayed impaired integrity and ultrastructure alterations in their colonic mucosa, which was characterized by diminished microvilli, mitochondrial swelling and epithelial cells apoptosis. Altered intestinal barrier function was linked to excessive apoptosis of IECs demonstrated by the higher proportion of TUNEL-positive apoptotic cells and enhanced caspase activities in BDNF(+/-) mice. Increased expression of Bax and claudin-2 proteins and reduced Bcl-2 and tight junction proteins (occludin, ZO-1 and claudin-1) expression were also detected in the colonic mucosa of BDNF(+/-) mice. BDNF may play a role in the maintenance of intestinal barrier integrity via its anti-apoptotic properties.

• MeSH
• apoptóza * MeSH
• epitelové buňky fyziologie   MeSH
• kaspasa 3 metabolismus   MeSH
• mozkový neurotrofický faktor fyziologie   MeSH
• myši inbrední C57BL MeSH
• myši knockoutované MeSH
• myši MeSH
• proteiny těsného spoje metabolismus   MeSH
• střevní sliznice metabolismus   ultrastruktura   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

A steady rise in the number of poly-sensitized patients has increased the demand for effective prophylactic strategies against multi-sensitivities. Probiotic bacteria have been successfully used in clinics and experimental models to prevent allergic mono-sensitization. In the present study, we have investigated whether probiotic bacteria could prevent poly-sensitization by imprinting on the immune system early in life. We used two recombinant variants of probiotic Escherichia coli Nissle 1917 (EcN): i) EcN expressing birch and grass pollen, poly-allergen chimera construct (EcN-Chim), and ii) an "empty" EcN without allergen expression (EcN-Ctrl). Conventional mice (CV) were treated with either EcN-Chim or EcN-Ctrl in the last week of the gestation and lactation period. Gnotobiotic mice received one oral dose of either EcN-Chim or EcN-Ctrl before mating. The offspring from both models underwent systemic allergic poly-sensitization and intranasal challenge with recombinant birch and grass pollen allergens (rBet v 1, rPhl p 1, and rPhl p 5). In the CV setting, the colonization of offspring via treatment of mothers reduced allergic airway inflammation (AAI) in offspring compared to poly-sensitized controls. Similarly, in a gnotobiotic model, AAI was reduced in EcN-Chim and EcN-Ctrl mono-colonized offspring. However, allergy prevention was more pronounced in the EcN-Ctrl mono-colonized offspring as compared to EcN-Chim. Mono-colonization with EcN-Ctrl was associated with a shift toward mixed Th1/Treg immune responses, increased expression of TLR2 and TLR4 in the lung, and maintained levels of zonulin-1 in lung epithelial cells as compared to GF poly-sensitized and EcN-Chim mono-colonized mice. This study is the first one to establish the model of allergic poly-sensitization in gnotobiotic mice. Using two different settings, gnotobiotic and conventional mice, we demonstrated that an early life intervention with the EcN without expressing an allergen is a powerful strategy to prevent poly-sensitization later in life.

• MeSH
• alergeny imunologie   MeSH
• alergie imunologie   MeSH
• antigeny rostlinné imunologie   MeSH
• bříza imunologie   MeSH
• epitelové buňky imunologie   MeSH
• Escherichia coli imunologie   MeSH
• gnotobiologické modely imunologie   MeSH
• homeostáza imunologie   MeSH
• imunitní systém imunologie   MeSH
• lipnicovité imunologie   MeSH
• myši inbrední BALB C MeSH
• myši MeSH
• probiotika aplikace a dávkování   MeSH
• pyl imunologie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The airway epithelium restricts the penetration of inhaled pathogens into the underlying tissue and plays a crucial role in the innate immune defense against respiratory infections. The whooping cough agent, Bordetella pertussis, adheres to ciliated cells of the human airway epithelium and subverts its defense functions through the action of secreted toxins and other virulence factors. We examined the impact of B. pertussis infection and of adenylate cyclase toxin-hemolysin (CyaA) action on the functional integrity of human bronchial epithelial cells cultured at the air-liquid interface (ALI). B. pertussis adhesion to the apical surface of polarized pseudostratified VA10 cell layers provoked a disruption of tight junctions and caused a drop in transepithelial electrical resistance (TEER). The reduction of TEER depended on the capacity of the secreted CyaA toxin to elicit cAMP signaling in epithelial cells through its adenylyl cyclase enzyme activity. Both purified CyaA and cAMP-signaling drugs triggered a decrease in the TEER of VA10 cell layers. Toxin-produced cAMP signaling caused actin cytoskeleton rearrangement and induced mucin 5AC production and interleukin-6 (IL-6) secretion, while it inhibited the IL-17A-induced secretion of the IL-8 chemokine and of the antimicrobial peptide beta-defensin 2. These results indicate that CyaA toxin activity compromises the barrier and innate immune functions of Bordetella-infected airway epithelia.

• MeSH
• adenylátcyklasový toxin genetika   metabolismus   toxicita   MeSH
• AMP cyklický metabolismus   MeSH
• Bordetella pertussis genetika   metabolismus   MeSH
• bronchy cytologie   metabolismus   mikrobiologie   MeSH
• cytoskelet metabolismus   MeSH
• epitelové buňky metabolismus   mikrobiologie   MeSH
• interleukin-6 metabolismus   MeSH
• lidé MeSH
• mucin 5AC metabolismus   MeSH
• pertuse genetika   metabolismus   mikrobiologie   MeSH
• signální transdukce účinky léků   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Outer membrane vesicles (OMVs) carrying virulence factors of enterohemorrhagic Escherichia coli (EHEC) are assumed to play a role in the pathogenesis of life-threatening hemolytic uremic syndrome (HUS). However, it is unknown if and how OMVs, which are produced in the intestinal lumen, cross the intestinal epithelial barrier (IEB) to reach the renal glomerular endothelium, the major target in HUS. We investigated the ability of EHEC O157 OMVs to translocate across the IEB using a model of polarized Caco-2 cells grown on Transwell inserts and characterized important aspects of this process. Using unlabeled or fluorescently labeled OMVs, tests of the intestinal barrier integrity, inhibitors of endocytosis, cell viability assay, and microscopic techniques, we demonstrated that EHEC O157 OMVs translocated across the IEB. OMV translocation involved both paracellular and transcellular pathways and was significantly increased under simulated inflammatory conditions. In addition, translocation was not dependent on OMV-associated virulence factors and did not affect viability of intestinal epithelial cells. Importantly, translocation of EHEC O157 OMVs was confirmed in human colonoids thereby supporting physiological relevance of OMVs in the pathogenesis of HUS.

• Publikační typ
• časopisecké články MeSH

• MeSH
• infekce dýchací soustavy imunologie   MeSH
• interleukin-17 imunologie   MeSH
• lidé MeSH
• organoidy imunologie   MeSH
• plíce imunologie   MeSH
• receptory interleukinu-17 imunologie   MeSH
• respirační sliznice imunologie   MeSH
• signální transdukce MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The choroid plexus (ChP) in each brain ventricle produces cerebrospinal fluid (CSF) and forms the blood-CSF barrier. Here, we construct a single-cell and spatial atlas of each ChP in the developing, adult, and aged mouse brain. We delineate diverse cell types, subtypes, cell states, and expression programs in epithelial and mesenchymal cells across ages and ventricles. In the developing ChP, we predict a common progenitor pool for epithelial and neuronal cells, validated by lineage tracing. Epithelial and fibroblast cells show regionalized expression by ventricle, starting at embryonic stages and persisting with age, with a dramatic transcriptional shift with maturation, and a smaller shift in each aged cell type. With aging, epithelial cells upregulate host-defense programs, and resident macrophages upregulate interleukin-1β (IL-1β) signaling genes. Our atlas reveals cellular diversity, architecture and signaling across ventricles during development, maturation, and aging of the ChP-brain barrier.

• MeSH
• analýza jednotlivých buněk MeSH
• buněčná diferenciace genetika   MeSH
• buněčný rodokmen genetika   MeSH
• epitelové buňky metabolismus   MeSH
• hematoencefalická bariéra metabolismus   MeSH
• mozek metabolismus   fyziologie   MeSH
• myši inbrední C57BL MeSH
• myši embryologie   MeSH
• nemoci mozku genetika   patofyziologie   MeSH
• plexus chorioideus embryologie   metabolismus   fyziologie   MeSH
• signální transdukce MeSH
• stárnutí fyziologie   MeSH
• věkové faktory MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši embryologie   MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH

The choroid plexus (CP) forming the blood-cerebrospinal fluid (B-CSF) barrier is among the least studied structures of the central nervous system (CNS) despite its clinical importance. The CP is an epithelio-endothelial convolute comprising a highly vascularized stroma with fenestrated capillaries and a continuous lining of epithelial cells joined by apical tight junctions (TJs) that are crucial in forming the B-CSF barrier. Integrity of the CP is critical for maintaining brain homeostasis and B-CSF barrier permeability. Recent experimental and clinical research has uncovered the significance of the CP in the pathophysiology of various diseases affecting the CNS. The CP is involved in penetration of various pathogens into the CNS, as well as the development of neurodegenerative (e.g., Alzheimer´s disease) and autoimmune diseases (e.g., multiple sclerosis). Moreover, the CP was shown to be important for restoring brain homeostasis following stroke and trauma. In addition, new diagnostic methods and treatment of CP papilloma and carcinoma have recently been developed. This review describes and summarizes the current state of knowledge with regard to the roles of the CP and B-CSF barrier in the pathophysiology of various types of CNS diseases and sets up the foundation for further avenues of research.

• MeSH
• homeostáza fyziologie   MeSH
• lidé MeSH
• mozkomíšní mok metabolismus   MeSH
• nemoci centrálního nervového systému * imunologie   metabolismus   patofyziologie   MeSH
• plexus chorioideus anatomie a histologie   fyziologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

BACKGROUND: Reduced microbial diversity has been associated with inflammatory bowel disease (IBD) and probiotic bacteria have been proposed for its prevention and/or treatment. Nevertheless, comparative studies of strains of the same subspecies for specific health benefits are scarce. Here we compared two Bifidobacterium longum ssp. longum strains for their capacity to prevent experimental colitis. METHODS: Immunomodulatory properties of nine probiotic bifidobacteria were assessed by stimulation of murine splenocytes. The immune responses to B. longum ssp. longum CCM 7952 (Bl 7952) and CCDM 372 (Bl 372) were further characterized by stimulation of bone marrow-derived dendritic cell, HEK293/TLR2 or HEK293/NOD2 cells. A mouse model of dextran sulphate sodium (DSS)-induced colitis was used to compare their beneficial effects in vivo. RESULTS: The nine bifidobacteria exhibited strain-specific abilities to induce cytokine production. Bl 372 induced higher levels of both pro- and anti-inflammatory cytokines in spleen and dendritic cell cultures compared to Bl 7952. Both strains engaged TLR2 and contain ligands for NOD2. In a mouse model of DSS-induced colitis, Bl 7952, but not Bl 372, reduced clinical symptoms and preserved expression of tight junction proteins. Importantly, Bl 7952 improved intestinal barrier function as demonstrated by reduced FITC-dextran levels in serum. CONCLUSIONS: We have shown that Bl 7952, but not Bl 372, protected mice from the development of experimental colitis. Our data suggest that although some immunomodulatory properties might be widespread among the genus Bifidobacterium, others may be rare and characteristic only for a specific strain. Therefore, careful selection might be crucial in providing beneficial outcome in clinical trials with probiotics in IBD.

• MeSH
• Bifidobacterium klasifikace   fyziologie   MeSH
• dendritické buňky mikrobiologie   patologie   MeSH
• HEK293 buňky MeSH
• imunoenzymatické techniky MeSH
• kolitida chemicky indukované   prevence a kontrola   MeSH
• lidé MeSH
• modely nemocí na zvířatech * MeSH
• myši inbrední BALB C MeSH
• myši MeSH
• probiotika farmakologie   MeSH
• signální adaptorový protein Nod2 genetika   metabolismus   MeSH
• síran dextranu toxicita   MeSH
• střeva mikrobiologie   patofyziologie   MeSH
• toll-like receptor 2 genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH